Two brain sites for cannabinoid reward

The recent findings that ^Δ9tetrahydrocannabinol ( ^Δ9THC), the active agent in marijuana and hashish, (1) is self-administered intravenously, (2) potentiates the rewarding effects of electrical brain stimulation, and (3) can establish conditioned place preferences in laboratory animals, suggest that these drugs activate biologically primitive brain reward mechanisms. Here, we identify two chemical trigger zones for stimulant and rewarding actions of ^Δ9THC. Microinjections of ^Δ9THC into the posterior ventral tegmental area (VTA) or into the shell of the nucleus accumbens (NAS) increased locomotion, and rats learned to lever-press for injections of ^Δ9THC into each of these regions. Substitution of vehicle for drug or treatment with a cannabinoid CB₁ receptor antagonist caused response cessation. Microinjections of ^Δ9THC into the posterior VTA and into the posterior shell of NAS established conditioned place preferences. Injections into the core of the NAS, the anterior VTA, or dorsal to the VTA were ineffective. These findings link the sites of rewarding action of ^Δ9THC to brain regions where such drugs as amphetamines, cocaine, heroin, and nicotine are also thought to have their sites of rewarding action.