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The Journal of Neuroscience, May 3, 2006, 26(18):4901-4907; doi:10.1523/JNEUROSCI.3554-05.2006

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Behavioral/Systems/Cognitive
Two Brain Sites for Cannabinoid Reward

Abraham Zangen,^1,2 * Marcello Solinas,^1 * Satoshi Ikemoto,¹ Steven R. Goldberg,¹ and Roy A. Wise¹

¹National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, and ²Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel

Correspondence should be addressed to Roy A. Wise, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224. Email: rwise{at}intra.nida.nih.gov

The recent findings that ⁹tetrahydrocannabinol (⁹THC), 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 ⁹THC. Microinjections of ⁹THC 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 ⁹THC into each of these regions. Substitution of vehicle for drug or treatment with a cannabinoid CB₁ receptor antagonist caused response cessation. Microinjections of ⁹THC 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 ⁹THC to brain regions where such drugs as amphetamines, cocaine, heroin, and nicotine are also thought to have their sites of rewarding action.

Key words: THC; reward; locomotion; ventral tegmental area; nucleus accumbens; self-administration

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Received March 9, 2004; revised March 26, 2006; accepted March 27, 2006.

Correspondence should be addressed to Roy A. Wise, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224. Email: rwise{at}intra.nida.nih.gov

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