Thesis final copy

DRUG DISCRIMINATION FORAGING

Discriminative Stimulus Effects of Nicotine during a Foraging Analysis

Caitlan Byrnes

Saint Anselm College

November 2014

Acknowledgments


I would like to take this time to thank those who helped me progress and complete this

experiment. I would like to especially thank Professor Troisi for aiding my studies and providing

me with necessary knowledge and equipment. I would also like to take this time to thank Sam

Dalhberg for caring for the laboratory animals!

Abstract


Animal models of drug discrimination have served as a backbone for human research concerning

addiction for centuries. Nicotine, a commonly used drug worldwide, can increase behaviors that

result in a delivery of non-drug reinforcers. Consequently, nicotine has primary reinforcing ef-

fects and can strengthen operant behaviors that lead to a delivery of rewarding stimuli such as

food or water (Bevins & Palmatier, 2004). The intent of the performed study was to define nico-

tine as a modulator for foraging behavior and then acquisition laboratory animals to associate a

particular drug state with a reward (water). The study begins with some introductory knowledge

essential for understanding and interpreting results by utilizing four subheadings; Conditioning:

Operant and Pavlovian, Drug Discrimination, Foraging and Practical Applications of use.

Throughout investigation different tandem sequences of nicotine and saline were expected to es-

tablish discriminative stimulus control over spatial learning for four rats, resulting in a decreased

latency time during a foraging analysis. It was predicted that the rate of voluntary responses

would become more frequent in an SD drug sequence because it occasions a response-reinforcer

relationship by reinforcing a behavior under a particular stimulus. Although results did not hold

significance between the independent and dependent variables, further research is suggested to

investigate modulation of behaviors using interoceptive cues. Internal cues are critical to addic-

tion and relapse behavior because internal or external stimuli may trigger a neurological response

within the brain that then may signal drug onset cues which when eliminated might lead to more

successful drug treatments. One theory for drug addiction is that if we change the context inter-

nally and externally we may decrease associations between the two which elicits relapse behav-

iors.

Table Of Contents

Acknowledgments ...................................................................................... Pg 2


Abstract ...................................................................................................... Pg 3

Introduction ...................................................................................................... Pg 6

Conditioning: Operant and Pavlovian …………………………………. Pg 6

Drug Discrimination.....................................................................………. Pg 7

Foraging.................................................................................................… Pg 9

Practical Applications.....................................................................……… Pg 9

Method ...................................................................................................... Pg 10

Subjects .......................................................................................... Pg 10

Aparatus .......................................................................................... Pg 10

Procedure .......................................................................................... Pg 11

Results ...................................................................................................... Pg 13

Discussion ...................................................................................................... Pg 15

Tables and Figures .......................................................................................... Pg 17

Table 1: “ Latency to first cap” ............................................................... Pg 17

Table 2: “Latency to last cap”................................................................. Pg 19

Figure 1: “Latency to first cap in seconds-rat 1” .................................... Pg 17




Figure 5: “Latency to last cap in seconds-rat 1” .................................... Pg 19





References ...................................................................................................... Pg 21

Appendices ...................................................................................................... Pg 23

Appendix A: “Morris water maze” ...................................................... Pg 23

Appendix B: “Syringes used” .................................................. Pg 24

Appendix C: “Water caps used” .................................................... Pg 25

Discriminative Stimulus Effects of Nicotine during a Foraging Analysis

As intelligent beings, it is natural to seek understanding regarding human behavior. As a

result, animal models have become a backbone attempting to parallel human addiction responses.

Many studies attempt to mirror human addiction behavior such as drug foraging where one phys-


ically goes through specified rituals to obtain a substance (Grund,1993). This is caused by an as-

sociation made between an internal or external stimuli which then triggers a neurological re-

sponse within the brain that may signal drug onset cues. When eliminated, an individual may be

less likely to relapse resulting in more successful drug treatments. One theory for drug addiction

is that if we change the context internally and externally we may decrease associations between

the two which elicits relapse behaviors (Siegel, Shepard & Ramos, 2002.) Another theory of

drug addiction is that our behaviors are driven by a series of learning processes in which we ac-

quire associations and modify our performance in response to a stimulus.

Conditioning: Operant and Pavlovian

Classical conditioning, is a psychological learning process that develops through associa-

tions made between an environmental stimulus and an internal or naturally occurring stimulus

(Kimble,1967). This theory of learning, first introduced by physiologist Ivan Pavlov, involves

pairing a sensory event to something biologically important, yielding a response. Pavlov sug-

gests that organisms are capable of tracking cues that predict natural recourses such as food, es-

pecially when under restricted conditions. In his study, “Pavlov’s Dogs” excitation occurs when

a neutral stimulus with no associations to a behavior (NS) is placed before a naturally occurring

reflex. From this research, psychologists have concluded that associative connections made be-

tween stimuli and the environment, help shape behavior. As a result, behavior is a reflexive so-

cial cue, eliciting a response when aroused by a specific stimuli (Mazur, 2002).

Behaviorism is a branch of Psychological thought that attempts to quantify, train, and al-

ter behavior through a modification process (Krantz, 2013). Operant conditioning, first coined by

B.F Skinner, is the second psychological theory used to describe behavioral learning. It proposed

that an organism is capable of modifying its behavior by associating that specific behavior to a


series of rewards or punishments (Mazur, 2002). One may acquire these associations through ob-

servational learning, language or rule governed schedules, or behavior modification which uti-

lizes adverse or reinforcement stimuli. Skinner described his theory of learning by presenting a

novel or spontaneous behavior and inhibiting or provoking that behaviors recurrence with posi-

tive/negative reinforcement or punishment. Neurologically speaking, this is due to an autonomic

response in the peripheral nervous system which when conditioned (CR) increases the action po-

tential along many motor neurons within the brain (Troisi, 2014). His research outlined the im-

portant relationship between internal and external stimuli and how external stimuli may be al-

tered to modify an organisms behavior. Skinner’s contribution to learning theory and his work

with animal models have crossed over into human studies concerning drug addiction and treat-

ment/therapy options.

Drug Discrimination

Research involving drug discrimination in rodent models, propose that a drug may serve

as an interoceptive cue suggesting the presence of a biologically important item such as food

(Troisi, 2014). An Interoceptive cue is a sensory response originating inside the body which then

may have an effect on behavior. In research on classical drug discrimination, nicotine functions

effectively as an operant discriminative stimulus. A “discriminative stimulus” (SD) occasions a

response-reinforcer relationship by reinforcing a behavior under a particular stimulus. An SD ,

can also serve as an “S.Delta” (SΔ) by signaling that a behavior has no consequence and will

likely reoccur (e.g., Troisi, Dooley, Craig, 2013; Troisi, Bryant, Kane, 2012). As a result, it has

been proposed that the function of a conditioned stimulus, or learned stimuli (CS) is not only to

signal the probability of an unconditioned stimuli (US), but also to serve as a spatial cue to guide

the animal in the environment (Blum & Abbott, 1996). Prior work (Davidson, Aparicio and


Rescorla, 1988) evidenced that operant discriminative stimuli and Pavlovian features function hi-

erarchically.

Nicotine, a commonly used drug worldwide, can increase behaviors that result in a deliv-

ery of non-drug reinforcers such as rewards or punishments. Consequently, nicotine has primary

reinforcing effects and can strengthen operant behaviors that lead to a delivery of encouraging/

rewarding stimuli such as food or water (Bevins & Palmatier, 2004). Hypothetically if this is

true, nicotine would enhance responding for strong reinforcers and may increase motivation to

obtain rewards associated with administration. Nicotine is also hypothesized to enhance sensory

properties such as taste, touch, or smell. Stimuli paired with nicotine and administered after in-

jections occur may have been altered by the drug and may increase the value of the reinforcer

(Troisi, 2014). The value of the reinforcer is essential to behavior consistency. In human drug ad-

diction studies, drug use is positive reinforcement and encourages behavior to reoccur because an

operant response (self-administration) directly produces a reinforcing effect through administra-

tion. When resources become scarce or looses is no longer contingent, foraging comes into play

to acquire the desired reward such as a drug/food.

Foraging

Foraging behaviors can be found in all organisms including humans. In the wild, foraging

behaviors reveal an organisms sensitivity to a specific stimuli in its environment. Foraging can

be considered an adaptive response to increase the likelihood of survival and is paralleled in ad-

diction studies as the drug seeking behavior that encourages relapse. When resources become

limited, behavior changes and the internal association between reduced reinforcement increases

behavioral variability (Gharib, Gade, & Roberts, 2004; Stahlman, Roberts, & Blaisdell, 2010).

According to the optimal foraging theory, an animal is expected to enter into a given activity de-


pending on associated costs and benefits (Arcis, 2003). Behavioral variation is critical to forag-

ing due to a decrease in resources which then promotes the stereotyping of a ritual to become

more successful during testing. In previous studies performed on primates, competition for re-

sources have behavioral consequences in females (Koenig, 2002) resulting in a reduced number

of offspring due to feeding competition. When a reward increases activity, extinction burst is

more likely to occur and this is what we know as relapse. Extinction burst is a phenomena in

which previously reinforced operant behaviors are no longer signaling the presence of a reward,

but the behavior continues to persist despite the absence of a reward Harris, Pentel, & LeSage,

2007). In human addiction studies this encourages behavioral variability to find access to more

reinforcers (drugs) which then spontaneously reinforces itself.

Practical Applications

Animal models act as a framework for human studies. It can be debated that many of our

medical achievements stem from laboratory research involving vertebrate animals. They give

psychologists a comparable organism to model human interactions involving molecules, cells,

and tissue responses. Studies involving interoceptive cues and drug addiction in animal and hu-

man models suggest that operant contingencies involving a response-reinforcement interaction

coincide with classical Pavlovian contingencies (Troisi, 2013).

If foraging behaviors were measured while using the drug discrimination paradigm previ-

ously mentioned, laboratory animals would be expected to show a rate of responding which

demonstrates a discrimination between a drug context in the SD condition which indicates food

or a biologically important resource and a saline condition and no reward; SΔ. It is expected that

internal cues, such as nicotine modulate foraging behaviors in laboratory animals based on a re-

ward/punishment system.

http://link.springer.com/search?facet-author=%22Andrew+C.+Harris%22

http://link.springer.com/search?facet-author=%22Mark+G.+LeSage%22

http://link.springer.com/search?facet-author=%22Mark+G.+LeSage%22

http://link.springer.com/search?facet-author=%22Paul+R.+Pentel%22


Method

Subjects

Test subjects involved four male Sprague Dawley rats who had no previous training in a drug

discrimination paradigm. The rats were not exposed to any drug internally or externally until the

study began on 9/11/14. The rats were 5 months old, originating from a private breeder and were

housed within the psychology department of a small liberal catholic college in the Northeast. The

animals were cared for daily under strict guidelines from the animal welfare from order of the

National Institute of Health (NIH) Committee. The subjects were housed two per cage (4x6”)

and were kept at a free-feeding weight throughout the study but were limited to 15 minutes of

water daily to keep thirst below satiation.

Apparatus

See Appendix A for complete visual of the “Morris Water Maze” (Morris et al. 1982). The Ap-

paratus is used to test Spatial learning, place learning, cognitive maps and memory through ob-

servation of a rat’s spatial cues to locate a specific object. The apparatus is a round circular en-

casement about 5 feet wide and 4.5 feet tall. Inside the apparatus is sawdust with 3 specific

“landmarks” such as wooden blocks to make quantifying behavior easier. Behavior as seen from

an experimenters point of view is difficult to quantify based on random movements the subject

makes. The blocks allow the researcher to determine how many times a subject returns to a spe-

cific spot with or without water. See Appendix B for image of a 10cc syringe which was used for

all injections required by this study. Drug doses were based on daily weights and the drug con-

sistency was a makeup of .08mgs of powdered Nicotine dissolved into a saline mixture. See Ap-

pendix C for visual of “water cap” used to contain 2ml of water (10mls total, 5 caps used). The


water caps were used to hold the reinforcer “water” under the SD drug condition depending on

the rat.

Procedure

The present study involves testing the discriminative stimulus effects of two drug sequences

(nicotine reinforced & saline not reinforced/ nicotine not reinforced&saline reinforced; NIC+ &

SAL-/ NIC- & SAL+); SD which sets the occasion for responding predicting the presentation of

water, and (nicotine not reinforced&saline reinforced/ nicotine reinforced&saline not

reinforced)NIC- & SAL+/NIC+ & SAL-); SΔ which is not paired with the reinforcer and does

not indicate a presentation of a reward (not predicting water). Four male Sprague Dawley rats

were water restricted to 15 minutes daily, to increase the value of the reinforcer during testing.

The study required the administration of counterbalanced drug conditions; nicotine according to

body weight(0.3mg/kg) and saline depending on whether they were SD or SΔ conditions. For

two rats, (rats 2 and 4) nicotine will function as an SD in which the presence of NIC was hypoth-

esized to increase behaviors and indicate a reward (water). For the other two rats (1 and 3), con-

ditions were counterbalanced and saline functioned as an SΔ which was not reinforced. Before

injection, fill the syringes accordingly to weight allowing 12 minutes for the drug onset period to

set in. Once administered through injection underneath the abdomen, the laboratory animals were

placed separately into the Morris pen at the same start location every time (to keep context as

controlled as possible). Within the pen were strategically placed water bowls or no reward/empty

caps (depending on the condition) along with 3 checkmarks such as a wooden block to serve as

landmarks within the apparatus. There were 5 caps containing 2ml of water each allowing the rat

to obtain 10ml of water during one session. The landmarks provided the primary investigator

with a systematic application of quantifying the rat’s behavior. This was defined by the rats turn-


ing behaviors, locomotion, returning behaviors etc. Locomotion was defined by the movement or

the ability of the subject to move from one place to another. Turning and returning behaviors

were based on the quantity of times a subject returned to a checkpoint for investigation. For par-

ticipants in the SΔ condition there was a 10minute foraging period in which behaviors were mea-

sured and compared to that of rats in the SD condition. Rats on test days were drugged or non-

drugged but water (the reward) was not present within the apparatus. The rats were placed into

the apparatus for a period of 5 minutes and were not rewarded to measure behavioral increases/

changes/etc. Behavioral increases were measured using latency times on a stopwatch to deter-

mine how quickly a subject could locate a water cap under a particular condition.

Results

The intent of the performed study was to define nicotine as a modulator for foraging be-

havior and then acquisition the laboratory animals to associate a particular drug state with a re-

ward (water). Throughout investigation different tandem sequences of nicotine and saline estab-

lished discriminative stimulus control over spatial learning and as a result decreased latency

times during the foraging analysis. It was predicted that the rate of voluntary responses would be

higher in a sequence during the SD condition because it occasions a response-reinforcer relation-

ship by reinforcing a behavior under a particular stimulus. The two dependent measures in the

performed study were the latency in minutes to the first and the last water cap over a series of

sessions. The independent variables were SD and SΔ drug conditions. Latency times were then

evaluated to reveal whether shorter latency times were paired with rats receiving the SD condi-

tion, despite which drug was being reinforced during that interoceptive state. The data collected


occurred over a period of 15 sessions and describe latency of each rat to the first cap found in the

foraging space. -------See Table 1------Following the collected data is a figure which describes

the relationship of rat one who received nicotine in the SΔ drug condition. ------See Figure

1-------- The figure illustrates rat 1’s latency to find the first cap in seconds. The table shows no

significant correlation, ether positive or negative that would suggest that nicotine is modulating

foraging behavior. During sessions 5-8, and 12-15 the figure demonstrates that rat one may have

had a slight behavior modification. During session 5 to session 6, saline was reinforced and la-

tency times decreased suggesting that an association between the drug and reward was made. Rat

2 received the opposite drug state in which nicotine was reinforced in the SD condition.--------

See Figure 2--------The figure shows again no consistent pattern or trend to prove or disprove the

original hypothesis, however between sessions 5-6 and 14-15 their is a decrease in response la-

tency to the first cap. This may suggest that nicotine is modulating latency behaviors and is de-

creasing the amount of time it takes for a subject to find the first cap. In figure 3, rat 3 continues

to show no significant pattern of response under the same condition as rat one. ------See Figure

3------ In Figure 4 the fourth rat’s latency to respond to the first cap is also shown. Rat 4 received

the same internal drug state as rat 2.------See Figure 4-------The figure shows a peculiar relation-

ship during sessions 5-8 because saline was not reinforced but responding decreased when it

should have increased. Sessions 8-9 showed a significant decrease in responding under a re-

warded condition (nic+) however, their was no consistent trend in behavioral responding.

Table 2 describes the latency in minutes of all four rats to retrieve the last cap of water

within the apparatus. -----See Table 2-------- Figure one demonstrates a latency of responding for

rat 1 that does not a significant trend. For rat 1 during sessions 7-9 , the primary observer de-

tected a decrease in latency for responding during the SΔ condition when their should have been


an increase. ----See Figure 5----- In later sessions, specifically sessions 14-15, rat one showed an

increased latency for responding while under the SD condition when according to the hypothesis

should have showed a decrease in responding. Rat 2 continued to show no significant trend of re-

sponding to the last cap. ----See Figure 6----- In Figure 6, rat 2 demonstrated a decreased latency

under the SD condition in sessions 7-8, however responding increases around session 10 and

continued to increase until session 15. Rat 3 had no trend in significant behavior. The latency for

responding under a saline reinforced state fluctuated over the 15 sessions however, from sessions

3-6, the latency for finding all 5 water caps has the potential to start showing a negative trend

(decreased latency times). This would agree with the hypothesis that the internal drug state,

whether saline or nicotine may play a role in fluctuating behavioral foraging. During session 12,

-----See Figure 7-------rat 3 increased latency time when saline was administered, again going

against the original hypothesis. The final rat began to show significant results according to figure

8 by having a continuous decrease in latency, however rat 4 showed a decrease in latency under

both conditions. ---See Figure 8---- Around session 11, behavioral variability increases and the

laboratory animal increased its rate of responding when it should have continued to decrease. Af-

ter consultation with several academic superiors, no inferential tests were performed. Because a

t-test compares means between subjects and variables, and their are only four subjects and 2 in-

dependent and 2 dependent variables, an inferential analysis will yield no extra information re-

garding significance of the study (Personal Consultation; P. Finn, 2014).

Discussion

Results gathered over 15 ten minute sessions, conclude that although nicotine has en-

hanced responding to strong reinforcers in past, it may not directly modulate foraging behaviors

during an analysis. Previous work (Palmatier, O’Brien, & Hall, 2011), recognizes several of the


confounding issues with this study. Their results suggested that the reinforcement enhancing ef-

fects of nicotine depend on conditioning history as well as behavioral motivation for the pre-

sented stimuli. The original hypothesis for the foraging analysis attempts to combine the enhanc-

ing effects of nicotine with a satiated stimulus to measure responding under each condition. Al-

though results showed little significance, their were several methodological flaws worth noting

that may have affected results. The laboratory animals were tested by the primary investigator

daily over a period of about two months. The testing however, did not reoccur consistently at the

same time every day. This may have affected results because of the animals feeding schedule.

The animals were watered for 15 minutes daily around 530pm, and if testing was performed right

before watering experimenters may be accidentally increasing the value of the reinforcer and re-

sults may be less symbolic of the expected foraging behavior. If testing were performed right af-

ter watering, the animals perhaps lost motivation for a devalued reward and as a result, had in-

creased reaction times in the apparatus.

Research for this study is ongoing and serves as a potential pilot for other similar drug

studies. Further research should be done with more laboratory subjects, testing consistently at the

same time every day over a period of several months. The results did not yield any significant

trend, however nicotine should not be ruled out as an important internal cue that may modulate

behavior. From this study several human parallels can be made regarding drug treatment. If the

study is replicated and significance is found, this information will lead to more efficient and

faster drug treatments. This focuses on the internal issue of drug addiction, by taking away the

internal cue that suggests the presentation of a drug, motivation to self-administer will diminish

and drug seeking behavior will be inhibited.


Tables and Figures

Table 1: “Latency to first cap”Rat 1 Rat 3 Rat 2 Rat 4

Nic- Sal+ Nic- Sal + Nic+ Sal - Nic+ Sal -Session 1 2.49 0.18 0.4 1.57 Session 2 2 0.2 4.2 6.31 Session 3 5.2 3.5 0.3 2.24 Session 4 7 1.3 2.1 0.3 Session 5 1 0.48 0.35 2 Session 6 0.1 0.2 0.15 0.36 Session 7 0.26 0.1 0.04 2.38 Session 8 1.22 0.19 0.05 0.08 Session 9 0.17 0.18 0.28 2.01 Session 10 0.1 0.17 0.24 0.2 Session 11 0.09 0.18 0.1 3.07 Session 12 0.43 0.46 0.18 1.32 Session 13 2.11 1.36 0.17 0.1 Session 14 0.51 1.11 2.12 2.41 Session 15 0.08 0.02 1.06 1.39

Figure 1: Latency to first cap in seconds-rat 1


Figure 2: Latency to first cap in seconds-rat 2

Figure 3: “Latency to first cap in seconds-rat 3”

Figure 4: “Latency to first cap in seconds-rat 4”

Table 2: “Latency to last cap” Rat 1 Rat 3 Rat 2 Rat 4 Nic- Sal+ Nic- Sal + Nic+ Sal - Nic+ Sal -Session 1 8.23 7.18 9.29 9.59 Session 2 7.52 6.35 6.24 10


Session 3 8.54 10 10 5.47Session 4 10 8.25 7.31 5.59 Session 5 7.28 9.28 9.12 7.43 Session 6 6 4.24 8.59 8.34 Session 7 8.23 6.14 8.32 8.2 Session 8 6.05 5.49 5.23 6.34 Session 9 4.3 5.2 6.4 5.45 Session 10 8 4.2 7.43 5.32 Session 11 3.17 6.21 6.19 3.43Session 12 9.27 3.06 6.11 2.3 Session 13 8.23 6.19 5.42 7.59 Session 14 2.34 6.31 7.33 4.33 Session 15 5.17 3.16 8.29 5.2

Figure 5: “Latency to last cap in minutes- rat 1”

Figure 6: “Latency to last cap in minutes- rat 2”

Figure 7: “Latency to last cap in minutes-rat3”


Figure 8: “Latency to last cap in minutes-rat4”


References

Arcis, V. V., & Desor, D. D. (2003). Influence of environment structure and food availability on

the foraging behavior of the laboratory rat. Behavioural Processes, 60(3), 191-198.

Bevins, R. A., & Palmatier, M. I. (2004). Extending the role of associative learning processes in

nicotine addiction. Behavioral and cognitive neuroscience reviews, 3(3), 143-

158.

Blum, K. I., & Abbott, L. F. (1996). A model of spatial map formation in the hippocampus of the

rat. Neural Computation, 8(1), 85-93.

Gharib, A., Gade, C., & Roberts, S. (2004). Control of variation by reward probability. Journal

of Experimental Psychology: Animal Behavior Processes, 30(4), 271.

Grund, J-P.C.. (1993, March 16). Drug use as a social ritual. Instituut voor Verslaving-

sonderzoek, Rotterdam.

Harris, A. C., Stepanov, I., Pentel, P. R., & LeSage, M. G. (2012). Delivery of nicotine in an

extract of a smokeless tobacco product reduces its reinforcement-attenuating and dis-

criminative stimulus effects in rats. Psychopharmacology, 220(3), 565-576.

Kimble, G. A. (Ed.). (1967). Foundations of conditioning and learning.

Appleton-Century-Crofts.

Koenig, A. (2002). Competition for resources and its behavioral consequences among female

primates. International Journal of Primatology, 23(4), 759-783.

Krantz, D. L. (1971), THE SEPARATE WORLDS OF OPERANT AND NON-OPERANT

PSYCHOLOGY. Journal of Applied Behavior Analysis, 4: 61–70.

Mazur, James E. (2002) Learning and behavior (5th ed.). Upper Saddle River, NJ, US:

Prentice Hall/Pearson Education.


Morris, R.G.M. (1982). Spatial localization does not require the presence of local cues. Learning

and Motivation, 12, 239-260.

Palmatier, M. I., O’Brien, L. C., & Hall, M. J. (2012). The role of conditioning history and

reinforcer strength in the reinforcement enhancing effects of nicotine in rats. Psy-

chopharmacology, 219(4), 1119-1131.

Stahlman, W., & Blaisdell, A. P. (2011). Reward probability and the variability of foraging

behavior in rats. International Journal Of Comparative Psychology, 24(2),

168-176.

Troisi, J. R., II, Dooley, T, II, & Craig, E. (2013). The Discriminative stimulus effects of a

nicotine-ethanol compound in rats: extinction with the parts differs from the whole.

Behavioral Neuroscience, 127, 899-912.

Troisi, J. R., II (2013). Perhaps More Consideration of Pavlovian-Operant Interaction May

Improve the Clinical Efficacy of Behaviorally Based Drug Treatment Programs. The

Psychological Record, 63, The Psychological Record, 63(4), 863-893.

Troisi, J.R., II, Bryant, E., & Kane, J. (2012). Extinction of the discriminative stimulus effects

of nicotine with a devalued reinforcer: Reinstatement following revaluation. The Psy-

chological Record, 62, 707-718.

Siegel, Shepard; Ramos, Barbara M. (2002). Applying laboratory research: Drug anticipation

and the treatment of drug addiction. Experimental and Clinical Psychopharmacol-

ogy, Vol 10

(3), Aug 2002, 162-183.


Appendices

Appendix A: Morris Water Maze (Morris et al, 1982)


Appendix B. 10cc Syringe used for injections


Appendix C:

Documents

Thesis final copy