DELTA(9)-TETRAHYDROCANNABINOL EXCITES RAT VTA DOPAMINE NEURONS THROUGH ACTIVATION OF CANNABINOID CB1 BUT NOT OPIOID RECEPTORS

Behavioral, biochemical and recent electrophysiological data have incr easingly implicated the involvement of dopamine in the central actions of cannabinoid compounds. However, the site and mechanism by which ca nnabinoids stimulate dopamine systems has been somewhat controversial. Central opioid systems have also been suggested to play a role in som e cannabinoid-induced behaviors as evidenced by their attenuation in t he presence of the opioid antagonist naloxone. However, recent studies using the cannabinoid receptor-selective antagonist SR141716A suggest that the central actions of psychoactive cannabinoids are mediated pr incipally through activation of CB1 receptors. Using single cell elect rophysiological recordings in the rat we assessed the effects of both SR141716A and naloxone on Delta(9)-tetrahydrocannabinol (THC)-induced activation of ventral tegmental dopamine neurons. While dopamine cell firing was dose-dependently increased following cumulative dosing with Delta(9)-THC it was partially or completely inhibited following pretr eatment with 0.5 and 2 mg/kg SR141716A, respectively. However, 1 and 1 0 mg/kg naloxone failed to alter the response to Delta(9)-THC. These d ata provide the first evidence that Delta(9)-THC-induced changes in me solimbic dopamine neuronal activity are mediated by the CB1 cannabinoi d receptor, but a causal link for the involvement of opioid systems co uld not be established. (C) 1997 Elsevier Science Ireland Ltd.