Two Brain Sites for Cannabinoid Reward

Abstract

The recent findings that ⌬9 tetrahydrocannabinol ( ⌬9 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 ⌬9 THC. Microinjections of ⌬9 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 ⌬9 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 ⌬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 ⌬9 THC to brain regions where such drugs as amphetamines, cocaine, heroin, and nicotine are also thought to have their sites of rewarding action.

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

“…The anandamide hedonic hotspot identified here completely covered that opioid hedonic hotspot in the dorsal rostral quadrant, and possibly extended beyond it caudally throughout most of the dorsal half of medial shell. We did not observe rostrocaudal differences for anandamide effects in medial shell here, unlike for previously reported reward-related effects of opioid, GABA, glutamate, and D 9 -THC microinjections in medial shell Berridge, 2002, 2003;Peciña and Berridge, 2005;Zangen et al, 2006). However, we caution that it may be premature to draw strong conclusions about precise relative boundaries of endocannabinoid vs opioid hotspots, or about the existence or lack of endocannabinoid rostrocaudal effects, because we mapped larger Fos plumes here than in the previous opioid mapping study.…”

“…Reward-related effects of anandamide are often viewed to be mediated by CB1 receptors (Piomelli, 2003;Cheer et al, 2004;De Vries and Schoffelmeer, 2005;Gardner, 2005;Kirkham, 2005;Thornton-Jones et al, 2005;Zangen et al, 2006). However, other CB receptor and even nonreceptor neuronal targets have been proposed for anandamide, some of which are present in the accumbens shell (for reviews, see Di Marzo et al, 2002;Pertwee, 2005).…”

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

“…While the hippocampus does play a role in the acquisition of contextual conditioning to various drugs (Meyers et al, 2006;Sharifzadeh et al, 2006), forming a link between lesser place aversion to THC in adolescent rats and hippocampal proteomic changes is difficult given that proteomic analysis occurred 3 weeks after place conditioning and at a time when the adolescent rats had reached adulthood. Analysis of the proteomic effects of acute cannabinoid treatment in adolescent and adult rats would clearly be an interesting follow-up study and might usefully examine nonhippocampal sites implicated in cannabinoid-reward, such as mesolimbic regions (Zangen et al, 2006).…”

Dual Role of Medial A10 Dopamine Neurons in Affective Encoding

“…Conditioned place preference has been shown to depend on stimulus-positive incentive learning (Perks and Clifton, 1997;Yin and Knowlton, 2002). In addition, rats learn to lever-press for administration of cocaine or amphetamine into the ventromedial striatum (Ikemoto, 2003;Ikemoto et al, 2005), and various other drugs into medial A10 Zangen et al, 2002Zangen et al, , 2006Rodd et al, 2004;Ikemoto et al, 2006). Further, blockade of dopamine receptors or lesions of dopaminergic terminals in the ventromedial striatum, but not the ventrolateral striatum, disrupts the establishment of conditioned place preference induced by systemic administration of cocaine, amphetamine, nicotine, or morphine (Sellings and Clarke, 2003;Fenu et al, 2006;Sellings et al, 2006a, b;Spina et al, 2006).…”