MESOLIMBIC DOPAMINERGIC DECLINE AFTER CANNABINOID WITHDRAWAL

The mesolimbic dopamine system has recently been implicated in the lon g-term aversive consequences of withdrawal from major drugs of abuse. In the present study we sought to determine whether mesolimbic dopamin e neurons are involved in the neurobiologic mechanisms underlying with drawal from chronic cannabinoid exposure. Rats were treated chronicall y with the major psychoactive ingredient of hashish and marijuana, Del ta(9)-tetrahydrocannabinol (Delta(9)-THC). Administration of the canna binoid antagonist SR 141716A precipitated an intense behavioral withdr awal syndrome, whereas abrupt Delta(9)-THC suspension failed to produc e overt signs of abstinence. In contrast, both groups showed a reducti on in dopamine cells activity as indicated by extracellular single uni t recordings from antidromically identified mesoaccumbens dopamine neu rons. The administration of Delta(9)-THC to spontaneously withdrawn ra ts restored neuronal activity. Conversely, SR 141716A produced a furth er 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 dop aminergic transmission in the limbic system, similar to that observed with other addictive drugs; these changes in neuronal plasticity may p lay a role in drug craving and relapse into drug addiction.