Rag. Neurd’sychophmacd 6 Bid. Psychiot 19f13. Vol. 7. pp. 487-483 Prtnted tn Great Brttain. All tihtr reserved.

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DOPAMJNERGIC lNv0LvEMmT IN THE CONTBOL OF DUNKING BBHAVIOUB: A BBIEF REVIEW

COLIN T. DOUKISH

Psychiatric Research Mvision, University of Saskatchewan Saskatoon, Saskatchewan, Canada

(Final form, July, 1983)

Contents

Abstract 487

1. Introduction 487

2. Lesion Studies of Dopamine Pathways and Thirst 488 3. Pharmacological Studies of Dopamlne and Thirst 488

A. Effects of Dopamine Agonists on Drinking 488 B. Effects of Dopamine Antagonists on Drinking 490

4. Conclueione 491 Acknowledgements 491

References 491

Abstract

Dourieh, Colin T.: Dopaminergic Involvement in the Control of Drinking Behaviour: A Brief Review. Prog. Neuro-Peychopharmacol. 6 Biol. Psychiat. 1983, 1(4-6) :487-493. 1. This paper briefly reviews the role of the neurotransmitter dopamIne (DA) in thirst and

drinking behaviour. 2. Electrolytic lesions of the lateral hypothalamus or 6-OHDA lesions of the nigro-striat-

al DA pathway produce aphaghia and adipsia. Similarly, DA receptor blockade inhibits drinking whereas the administration of DA or DA agonists can facilitate drinking.

3. The involvement of DA in thirst is discussed with respect to the mediation of the motivational and motor responses associated with drinking behaviour.

Keywords: adipsia, dopamine, drinking behaviour, thirst, water deprivation

Abbreviations: dopamine (DA), intracerebroventricular (TCV), intraperitoneal (IP), lateral hypothalamus (LH), monoamine oxidase inhibitor (MAOI), 6-hydroxydopamine (6-OHDA)

1. Introduction

In recent years, there has been extensive investigation of the role of brain dopamine (DA) neuronee in the neural regulation of feeding and reward processes (see reviews by Leibowitr 1980, Wine 1981). However, relatively little attention hae been paid to the role of DA in thirst and drinking behaviour. The poesible Involverent of DA in thiret was first euggceted by the discovery of Dngeratedt (1971) that bilateral 6-hydroxydopamine (6+HDA) leeione of the DA neurones which arise in the subetantia nigra and ascend to innervate the caudate-putapen (the nigo-atriatal pathway) produced a syndrome of aphagia and adipeia in

487

488 C.T. Dourish

rats. This 6-OEDA-induced syndrome was similar in many respects to the aphagia and adipsia of the lateral hypothalamic syndrome produced by bilateral electrolytic lesions of the lateral hypothalamus (LH) and first described by Anand and Brobeck (1951).

2. Lesion Studies of Dopamine Pathways and Thirst

Following the seminal work of Anand and Brobeck (1951) the LH became an important focus of attention in the study of the neural control of feeding and drinking. In subsequent studies (reviewed by Epstein 1971) Teitelbaum and his colleagues demonstrated that LH lesioned rats which were initially aphaglc and adipsic could be kept alive by tube feeding and progressed through a series of stages before eventually beginning to eat chow and drink water once again. However, the recovered animals exhibited permanent drinking deficits, In particular the loss of response to acute physiological challenges such as water deprivation or hypertonic saline injection. Furthermore, it was demonstrated that recovered rats only exhibit prandlal drinking since LH lesions impair salivary function and the animals drink only in order to be able to consume dry chow (Epstein 1971).

Ungerstedt (1971) and others subsequently (see review by Stricker and Zigmond 1976) post- ulated that the LH syndrome of aphagia and adipsia could be due to interruption of the nlgro-striatal DA neurones which ascend through the LH. Animals bearing 6-OHDA lesions of the nigro-striatal DA neurones exhibited profound aphagia and adlpsia and If kept alive by force feeding passed through the same series of recovery stages as LH lesioned animals (Stricker and Zigmond 1976). Furthermore, a number of studies were able to de onstrate a relationship between the extent of striatal DA depletion and the severity of adipsia (Stricker and Zigmond 1976). In addition to disruption of feeding and drinking however, nigro-strlatal C-OHDA lesions disrupt sensorimotor function and learning (Marshall and Teitelbaum 1977) and It appears likely that such brain damage could interfere with drinking by impairing the animals ability to initiate the appropriate behavioural response. There is now considerable evidence which suggests that interruption of the nigro-striatal DA pathway cannot fully account for the LH syndrome. The aphagia and adipsia produced by B-OHDA lesions is never as severe as that produced by LH lesions despite the fact that LH lesions produce a considerably smaller forebrain DA depletion than extensive 6-OHDA lesions (Stricker and Zigmond 1976). Furthermore, regulatory drinking responses can be restored by DA agonist treatment in 6-OHDA lesioned rats but not in rats with electrolytic LH lesions (Marshall and Ungerstedt 1976, Dourish and Jones 1982). In addition, recent studies util- izing the neurotoxins kainic acid and ibotenic acid (which destroy cell bodies but spare fibres of passage) have demonstrated that injection of these compounds into the LH induces aphagia and adipsia and permanent deficits in regulatory drinking responses (Grossman et al 1978, Tarbuck et al 1983). Such data strongly suggest that damage to neurones with cell bodies located within the LH must play an important role in the drinking impairments which are evident following electrolytic LH lesions. This is consistent with evidence from neurophysiological studies that neurones located in the LH respond to both the sight and taste of water whereas nlgro-striatal neurones respond to movement and may be involved in the initiation of motor movements required for drinking behaviour(Eolls and Bolls 1982).

3. Pharmacological Studies of Dopamine and Thirst

A. Effects of Dopamine Agonists on Drinking_

Investigations of the effects of increasing brain DA transmission on thirst have produced conflicting results (See Table 1 for a summary). Microinjection of DA into the brain of water replete rats or monkeys elicits a modest drinking response (Myers 1969, Fitzsimons and Setler 1975). Similarly, hypothalamic application of the DA agonist apomorphine has been reported to initiate drinking (Fisher 1973). In contrast, Neilsen and Lyon (1973) have reported that 0.8 mg/kg apomorphine given IP Inhibits drinking in water-deprived rats, an effect which can be reversed by neuroleptic pretreatment. However, it appears that this inhibition of drinking may be due to the production of lncompatable motor responses such as

Dopamine and drinking 489

hyperactivity and stereotypy which are associated with doses of 0.2-2.0 mg/kg apomorphine (Maj et al 1972).

Table 1

Effects of Dopamine and of Dopamine Agonists on Thirst

Compound Species Effeots on Thirst Reference

Dopamine Rat ICV injection elicits drinking in Fitzsimons & Setler (1975) water replete animals. Poat et al (1980)

Rat Application to perifornical LH suppresses drinking. Leibowitz & Rossakis (1979)

Monkey Hypothalamic application increases drinking in water replete animals. Myers (1969)

Apomorphine Rat Hypothalamic application elicits drinking in water replete animals. Fisher (1973) Acute IP injection of a high dose inhibits drinking induced by water-deprivation. Nielsen & Lyon (1973) Chronic IP Injection of low doses increases drinking induced by water-deprivation. Dourish & Cooper (1981b)

Piribedil Rat Acute IP Injection of high or low Dourish & Cooper (1978) doses inhibits drinking. Dourish & Cooper (1978) Chronic IP injection of low doses increases drinking Induced by water-deprivation. Dourish 6 Cooper (1981a)

L-Dopa Rat IP injectlon with nlalamide (an MAOI) inhibits drinking induced by water-deprivation. Soulairac & Soulairae (1970) IP injection with FLA-63 (a DA -hydroxylase inhibitor) in- creases drinking induced by food deprivation. Fitzsimons 6 Setler (1975)

Amphetamine Rat Acute IP injection of low doses Glick 6 Muller (1971) enhances hypertonic saline induced Dourish 6 Jones (1982) drinking and prandial drinking. Chronic IP injection of high doses increases drinking in water replete rats. Rowland et al (1981) IP injection of high doses acutely or chronically inhibits drinking. Soulairac 6 Soulairac (1970) Application to perifornical lateral hypothalamus suppresses drinking. Leibowltz (1973)

ICV = intracerebroventricular; IP = intraperitoneal; MAO1 = monoamine oxidase inhibitor.

Interestingly, small doses of apomorphlne (15-125 ug/kg) can facilitate an ongogng drink- ing response in rats which have been water deprived (Dourish and Cooper 1981b). Similarly, another DA agonist piribedil indirectly suppresses drinking by inducing stereotypy and hyperactivity at high doses (Dourish and Cooper 1978) or sedation at low doses (Wurlsh and Cooper 1982) but produces an elevation in deprivation-induced drinking when administered chronically at low doses (Dourlsh and Cooper 1981a). Such data may be interpreted as support for a possible faclliatory role of DA in drinking responses.

490 C.T. Dourish

The effects of amphetamine on water intake have been extensively investigated but the data are conflicting (see Table l), since the drug has been reported to increase and decrease drinking in various paradigms (for further discussion see Leibowitz 1980).

B. Effects of Dopamine Antagonists on Drinking

The effects of DA antagonists on drinking are summarized in Table 2. The use of neuro- leptics to investigate the role of DA in drinking suffers from the same problem associated with studies of the effects of neuroleptics on feeding and reward (ie. the differentiation of motivational and motor effects, see Leibowitz 1980, Wise 1981). However, there is some evidence which suggests that neuroleptic-induced suppression of water intake may not simply be secondary to motor impairments. Neuroleptics administered either peripherally or cen- trally are particularly effective antagonists of drinking induced by the peptide angiotens- in II (Fitzsimons and Setler 1975, Sumners et al 1979) or by lithium (Mailman 1983) whereas drinking induced by the cholinergic agonist carbachol is generally unaffected by DA recep- tor blockade (see Table 2). Similarly, 6-GRDA induced depletion of brain catecholamine content attenuates the drinking response to angiotensin or lithium but has no effect on the response to carbachol (Fitzsimons and Setler 1975, Sumner8 et al 1979, Mailman 1983).

Table 2

Effects of Neuroleptics on Thirst

Compound Species Effects on Thirst Reference

Baloperidol Rat Central application to hypothal- amus, septum, pre-optic or ventricle suppresses drinking induced by angiotensin or water- deprivation. Peripheral injection suppresses drinking induced by angiotensin, lithium, renin, hypovolemia or isoprenaline.

Monkey ICV injection attenuates angiotensin-induced drinking.

Fitzsimons & Setler (1975) Peres et al (1974) Fisher (1973) Sumners et al (1979)

Fisher (1973), Rowland 6 Engle (1977), Sumners et al (1979), Casner et al (1975), Block and Fisher (1975), Mailman (1983)

Fisher & Buggy (1975)

Spiroperidol Rat Application to pre-optic or nucleus accumbens blocks drink- Fitzsimons & Setler (1975) ing induced by angiotensin but Jones & Mogenson (1982) not carbachol.

Rat IP injection attenuates Rolls et al (1974) deprivation-induced drinking. Rowland 6 Engle (1977)

Pimozide

Sulpiride

Rat IP injection suppresses Ungerstedt (1971), Nielsen deprivation-induced drinking. & Lyon (1973), Grupp (1976)

Rat ICV application blocks drinking Sumner6 et al (1979) induced by angiotensin but not carbachol.

Chlorpromazine Rat ICV application blocks drinking Sumner8 et al (1979) induced by angiotensin but not carbachol. IP injection attenuates drinking De Wied (1966), Falk & induced by angiotensin, hyper- Burnidge (1970), Schmidt h tonic saline, carbachol and Moak (1958), Lehr (1973) isoprenaline.

Dopamine and drinking 491

Conversely, chronic neuroleptic treatment which results in DA receptor supersensitivity in- creases angiotensin-induced drinking without altering the response to carbachol (Sumners et al 1981). On the basis of such data it has been proposed that nigro-striatal DA neurones may be importantly involved in the control of the polydipsia induced by angiotensin and lithium (Fitzsimons and Setler 1975, Sumners et al 1981, Mailman 1983).

Interestingly, recent studies have suggested that mesolimbic DA neurones may be essential for the maintenance of drinking. Injections of spiroperidol into the nucleus accumbens produced decreases in lap volume, tongue extension and volume of water consumed in water- deprived rats. Similar applications of spiroperidol to the striatum had no effect on these measures (Jones and Mogenson 1979). This suggests that one function of the mesolimbic DA system may be to maintain oral motor performance during a drinking task. However, at lower doses spiroperidol increased latency to drink and decreased drinking in response to angio- tensin II, in the absence of oral motor deficits (Jones and Mogenson, 1982). These data are consistent with the proposed role of DA in the angiotensin thirst circuit (Fitasimons and Setler 1975, Sumner8 et al 1981).

4. Conclusions

The evidence reviewed in this paper suggests that the integrity of DA neurones is requir- ed for normal drinking behaviour. It is now clear that interruption of the nigrostriatal DA pathway is probably not the primary cause of the drinking deficits associated with extensive electrolytic lesions of the LPI. However, recent pharmacological, electrophysio- logical and behavioural data indicate that nigro-striatal and mesolimbic DA neurones may play an important role in the motor components involved in the initiation of drinking and in the maintenance of an ongoing drinking response. In addition, physiological and pharma- cological studies have suggested that DA neurones are involved in the neural regulation of the angiotensin thirst circuit. Although DA is clearly not the major neurotransmitter involved in the control of drinking it appears that DA neurones may play an important modulatory role in neural thirst mechanisms , particularly with regard to motor responses associated with drinking behaviour.

Acknowledgements

The author thanks Drs. S.J. Cooper and A.A. Boulton for advice and encouragement, the Department of Health, Province of Saskatchewan for continuing financial support, and Dr. S.B. Dunnett for providing access to unpublished data.

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