Showing papers by "Satoshi Ikemoto published in 2006"

Two Brain Sites for Cannabinoid Reward

Abstract: The recent findings that Δ9 tetrahydrocannabinol ( Δ9 THC), 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 Δ9 THC. Microinjections of Δ9 THC 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 Δ9 THC into each of these regions. Substitution of vehicle for drug or treatment with a cannabinoid CB 1 receptor antagonist caused response cessation. Microinjections of Δ9 THC 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 Δ9 THC to brain regions where such drugs as amphetamines, cocaine, heroin, and nicotine are also thought to have their sites of rewarding action.

Primary reinforcing effects of nicotine are triggered from multiple regions both inside and outside the ventral tegmental area.

Abstract: Nicotine is thought to be the key substance responsible for tobacco-smoking habits and appears to trigger reinforcement via the ventral tegmental area (VTA). Recently, multiple anatomical substrates for drug reinforcement have been identified in the vicinity of the ventral midbrain. In addition to the posterior portion of the VTA, the central linear nucleus raphe and the supramammillary nucleus of the posterior hypothalamus mediate drug reinforcement. Using intracranial self-administration procedures, we examined whether these regions mediate the reinforcing effects of nicotine. Rats learned to lever press for self-administration of nicotine into the posterior VTA, central linear nucleus, and supramammillary nucleus, suggesting a reinforcing action of nicotine in these regions. The rats did not self-administer nicotine into surrounding regions including the anterior VTA, substantia nigra, the region just dorsal to the posterior VTA, interpeduncular nucleus, or medial mammillary nucleus. The reinforcing effects of nicotine into the three brain regions were further confirmed by a two-lever discrimination procedure, in which rats learned to selectively respond between active and inactive levers. The reinforcing effects of nicotine administration into the posterior VTA, central linear nucleus, and supramammillary nucleus were blocked by coadministration of the nicotine receptor antagonist mecamylamine. The reinforcing effects of nicotine into the posterior VTA or central linear nucleus were attenuated by coadministration of the D2 receptor agonist quinpirole. These findings demonstrate that nicotine reinforcement involves multiple regions both inside and outside the VTA.