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THE LANCET Vol 356 December 9, 2000 1989

SCIENCE AND MEDICINE

What causes opiate tolerance?

Apossible cause for the develop-ment of opiate tolerance hasbeen proposed by a team of USresearchers this week. Mice lackingthe gene which codes for a regula-tory protein called -arrestin-2failed to develop tolerance to morphine, but did still become physically dependent on the drug.

Decreased responsiveness to anagonist has been correlated with thedesensitisation of G-protein recep-tors in a number of different systems. Previous in-vitro worksuggested that regulatory elementssuch as -arrestin-2 are involved in-opioid receptor desensitisation.However, the contribution of theseregulatory elements to the physio-logical regulation of the -opioidreceptor and to the development oftolerance in vivo was previouslyunsubstantiated, explains LauraBohn (Duke University, Durham

NC, USA), the lead invesigator ofthe new study (Nature 2000; 408:72023).

Interference with receptordesensitisation may prevent thedevelopment of opiate tolerance.However it does not prevent theonset of opiate dependence afterchronic use suggesting that themorphine-induced neurologicaladaptation behind each of theseevents differs in the regulatory con-trol of the receptor, says Bohn.

She speculates that by pharma-cologically targeting -arrestin-2,very low doses of morphine couldbe used to achieve potent analgesia.At the same time, the degree of opiate dependence may be reducedbecause the amount of drugrequired for daily pain relief couldbe greatly reduced.

Minal Chande

Speech and sign language trigger similar brain activity

Brain regions previously thoughtto be dedicated solely to makingsense of sound may in fact beinvolved in the processing of signlanguage as well, report Canadianresearchers. It seems that thisneural tissue possesses a unique sen-sitivity for aspects of language pat-terning [regardless of whether theinput is oral or visual], says leadauthor Laura Petitto (McGillUniversity, Montreal, Quebec).Deaf children learn sign languageon the same timetable as hearingchildren learn speechwhen a hear-ing child begins to babble vocally, adeaf child begins to babble manually.If the brain were so dependent onspeech, then why would deaf chil-dren achieve language normally?

Petitto and co-workers usedpositron emission tomography tocompare blood flow patterns in thebrains of 11 deaf and 10hearing people inresponse to five tasksinvolving signed(American SignLanguage or Languedes Signes Quebecoise)and spoken language.The left inferior frontalcortex, long thought tobe involved in theretrieval of spokenwords, was activatedwhen deaf people wereasked to generate mean-ingful signs. And theplanum temporale,

thought to be dedi-cated to the process-ing of speech sounds,showed increasedactivity in deaf peoplewhen they perceivedmeaningful signs andparts of signs that aresimilar to syllables ofspoken words (ProcNatl Acad Sci; 97:1396166).

Two possible con-clusions can be drawnfrom the findings,says David Caplan( M a s s a c h u s e t t sGeneral Hospital,

Boston, MA, USA), author of acommentary on the study. One isthat this bit of the brain which ordi-

narily does spoken lan-guage is actuallygenetically suited tohandle any kind of lan-guage in the primarymodality of languagelearning. The other isthat the symbols pre-sented visually forwords and non-wordsinvolve rapidly chang-ing configurations ofthe hands, and so thispart of the brain may beable to process any kindof stimulus that changesrapidly over time.

Now it would be possible to givethese deaf people complex, visually-presented material that changessequence quickly but is not reallylanguage, and see whether or not itlights up this area of the brain. If itdoesnt, they have a much strongercase that this area just does lan-guage, says Caplan. Either way,the evidence challenges the prevail-ing theory that this part of the brainis devoted to language processesbecause it analyses auditory input.And clinically, anything that docu-ments the brains plasticity is gener-ally good news for recovery.

Marilynn Larkin

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Pathway for intelligible speech identified A report and commentary in Brain (2000; 123:240006, 237172) indicate that the left superiortemporal sulcusnot the planum temporale, assuggested in the accompanying storyresponds to thepresence of speech-like sounds, and that the anteriorpart responds only if the sound is also intelligible. The finding raises the possibility that the brain areaactivated by sign language in the Canadian study isclose to, but not exactly the same as, the area devotedto speech perception in hearing people, commentsDavid Caplan (Massachusetts General Hospital,Boston, MA, USA). Its as if language processinggravitates towards the auditory association region, butuses different parts of this region depending uponother factors (ie, hearing or hearing deprivation).

Left inferior cortex involved

News in BriefNew therapy for stroke? A pilotstudy has shown the benefits of con-straint-induced movement (CIM)therapy for the treatment of stroke,even if the therapy does not startuntil 14 days after the stroke.Patients randomly assigned to theCIM group showed more improve-ment in overall arm strength andcoordination than patients whoreceived traditional therapy (Stroke2000; 31: 298488).

Hope in the fight against EbolaA sequence of four amino acids hasbeen identified in a key viral proteinthat may be critical to the transmis-sion of the Ebola virus. This discov-ery may facilitate the developmentof new medications to fight Ebola,according to the studys authors(Proc Natl Acad Sci 2000; 97:1387176).

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