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Mesolimbic dopaminergic decline after cannabinoid withdrawal

Diana, Marco and Melis, Miriam and Muntoni, Anna Lisa and Gessa, Gian Luigi (1998) Mesolimbic dopaminergic decline after cannabinoid withdrawal. Proceedings of The National Academy of Sciences, Vol. 95 (17), p. 10269-10273. eISSN 1091-6490. Article.

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The mesolimbic dopamine system has recently been implicated in the long-term aversive consequences of withdrawal from major drugs of abuse. In the present study we sought to determine whether mesolimbic dopamine neurons are involved in the neurobiologic mechanisms underlying withdrawal from chronic cannabinoid exposure. Rats were treated chronically with the major psychoactive ingredient of hashish and marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Administration of the cannabinoid antagonist SR 141716A precipitated an intense behavioral withdrawal syndrome, whereas abrupt D9-THC suspension failed to produce overt signs of abstinence. In contrast, both groups showed a reduction in dopamine cells activity as indicated by extracellular single unit recordings from antidromically identified mesoaccumbens dopamine neurons. The administration of Δ9-THC to spontaneously withdrawn rats restored neuronal activity. Conversely, SR 141716A produced a further decrease of spontaneous activity in cannabinoid-treated although it was ineffective in control rats. These data indicate that withdrawal from chronic cannabinoid administration is associated with reduced dopaminergic transmission in the limbic system, similar to that observed with other addictive drugs; these changes in neuronal plasticity may play a role in drug craving and relapse into drug addiction.

Item Type:Article
ID Code:1141
Uncontrolled Keywords:Mesolimbic dopamine system, withdrawal syndrome, Δ9-tetrahydrocannabinol (Δ9-THC)
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:The National Academy of Sciences of the USA
Publisher Policy:Depositato per gentile concessione dell'Editore. È vietato duplicare e postare il PDF. E' consentito l'uso a solo scopo di studio e di ricerca.
Deposited On:18 Aug 2009 10:04

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