In vivo microdialysis studies of Delta(9)-tetrahydrocannabinol's effects on dopamine systems within mesotelencephalic pleasure/reward circuits in the rat brain

Abstract

Among the many pharmacological properties of marijuana is a dose-dependent euphorigenic action deriving primarily from the psychoactive cannabis constituent {dollar}\Delta\sp9{dollar}-tetrahydrocannabinol ({dollar}\Delta\sp9{dollar}-THC). Marijuana is an abusable and habit-forming drug, and is presently the most commonly used illicit drug in North America and Europe.;Since much evidence has shown that the mesotelencephalic dopamine (DA) system plays an important role within the brain pleasure/reward circuits, the questions obviously arise: does {dollar}\Delta\sp9{dollar}-THC also act on the mesotelencephalic DA system like most other drugs of abuse? If yes, where dose this interaction occur within the mesotelencephalic DA system? What are the pharmacological mechanisms? The present study was designed to answer these questions by using the in vivo brain microdialysis technique in conscious, freely moving rats, combined with high performance liquid chromatography. The data indicate that acute {dollar}\Delta\sp9{dollar}-THC administration increases extracellular DA levels in the nucleus accumbens and medial prefrontal cortex, which are crucial terminals of the mesotelencephalic DA system. This DA-enhancing effect of {dollar}\Delta\sp9{dollar}-THC occurs at the DA terminals and is similar to that of such typical DA reuptake blockers as nomifensine. Also this DA-enhancing effect is naloxone-blockable, which suggests the involvement of an endogenous opioid system in the modulation of {dollar}\Delta\sp9{dollar}-THC's action on the activities of the mesotelencephalic DA system.