Cannabinoid Modulation of Opiate Reinforcement through the Ventral Striatopallidal Pathway

Abstract

Recent evidence indicates that cannabinoid-1 (CB 1 ) receptors play a role in the mediation of opiate reward, though the neural mechanisms for this process have not been characterized. The present experiments investigated the influence of CB 1 receptors in the ventral striatopallidal system on opiate-induced neurochemical events and opiate self-administration behavior in rats. Acute morphine administration (3 mg/kg) significantly reduced ventral pallidal GABA efflux in a manner similar to that produced by heroin selfadministration. This neurochemical effect was reversed by doses of the selective CB 1 antagonist SR 141716A (Rimonabant; 1 and 3 mg/kg) that also significantly reduce opiate reward. Morphine-induced increases in nucleus accumbens dopamine levels were unaltered by SR 141716A. Intravenous heroin self-administration (0.02 mg/infusion) was significantly reduced by intra-accumbens, but not intraventral pallidal SR 141716A infusions (1 and 3 mg/side), implicating nucleus accumbens CB 1 receptors in the modulation of opiate reinforcement. In contrast, SR14716A did not alter cocaine self-administration (0.125 mg/inf), cocaine-induced (10 mg/kg) decrements in ventral pallidal GABA efflux or cocaine-induced increases in accumbens dopamine. This is consistent with evidence that selective inactivation of CB 1 receptors reduces opiate-, but not psychostimulant-maintained self-administration. The CB 1 receptor agonist WIN 55,212-2 (5 mg/kg) reduced pallidal GABA efflux in a manner similar to morphine, and this effect was reversed by the opiate receptor antagonist naloxone. Collectively these findings suggest that CB 1 receptors modulate opiate reward through the ventral striatopallidal projection and that the modulation of this projection system may be involved in the reciprocal behavioral effects between cannabinoids, and opioids.

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

“…Anatomical overlap suggests the possibility that both endocannabinoid and opioid signals might act on the same local circuits to amplify hedonic impact. It is of interest that CB1 receptors and opioid receptors are reported to interact, can occur in the same striatal synapses, and even be colocalized on the same neurons in nucleus accumbens shell and core (Tanda et al, 1997;Hohmann and Herkenham, 2000;Rodriguez et al, 2001;Pickel et al, 2004;Caille and Parsons, 2006). If colocalization occurs in hotspot neurons, this would support the possibility that endocannabinoid and opioid neurochemical signals in nucleus accumbens might interact to enhance 'liking' reactions to the sensory pleasure of sucrose.…”

“…For example, a 1 mm 3 'hedonic hotspot' was recently found in the medial shell where m opioid receptor activation by DAMGO microinjections tripled positive 'liking' orofacial reactions that are elicited by sucrose taste in rats (Peciña and Berridge, 2005), and stimulated food intake (though the intake 'wanting' site extended further) (Bakshi and Kelley, 1993;Zhang and Kelley, 2000;Peciña and Berridge, 2005). Opioid and endocannabinoid neurotransmissions are known to positively interact (Tanda et al, 1997;Kirkham and Williams, 2001;Navarro et al, 2001;Rowland et al, 2001;Williams and Kirkham, 2002b;Verty et al, 2003;Solinas and Goldberg, 2005;Vigano et al, 2005;Caille and Parsons, 2006;Cota et al, 2006), raising the possibility that endocannabinoid receptor activation might increase 'liking' for natural rewards in the same hedonic hotspot of the medial accumbens shell where opioids do so.…”

Rimonabant Precipitates Anxiety in Rats Withdrawn from Palatable Food: Role of the Central Amygdala

“…Intraperitoneal and site-specific doses of rimonabant were chosen based on previous literature (Caille and Parsons, 2006;Dore et al, 2013b;Gessa et al, 2006;Roche et al, 2007).…”

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

“…Then, WIN55,212-2 (1 or 5 g in 0.5 l of vehicle) or vehicle (0.5 l) was continuously delivered for 3 min. In some cases, infusion of rimonabant [1 g (Caillé and Parsons, 2006) in 0.25 l of vehicle for 1.5 min] was performed 1 min before infusion of WIN55,212-2 (1 g in 0.25 l of vehicle for 1.5 min). In all groups, total infusion volume was 0.5 l. The microinfusion connector assembly was left in place 4 more min to allow the drug solution to diffuse into the target structure (mPFCv).…”