Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common µ ₁ Opioid Receptor Mechanism

Abstract

The effects of the active ingredient of Cannabis , Δ 9 -tetrahydrocannabinol (Δ 9 -THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis. Δ 9 -THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Δ 9 -THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of μ 1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Δ 9 -THC and heroin exert similar effects on mesolimbic dopamine transmission through a common μ 1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats

“…Such alteration in the mOR coupling would be expected to potentiate dopamine levels in forebrain areas such as the NAc and caudate-putamen, considering that stimulation of these midbrain receptors would disinhibit the inhibitory GABAergic regulation on dopamine cell firing (Johnson and North, 1992). The potential involvement of the dopamine system in regulating the long-term effects of THC should be directly addressed in future studies with the current animal model, but studies in the literature have already substantiated enhanced striatal dopamine levels following THC administration (Malone and Taylor, 1999;Tanda et al, 1997). Interestingly, heroin intake behavior was directly correlated with agonist activation of the mOR GTP coupling and this observation was specifically localized to the NAc shell.…”

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.…”

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

“…The effect of CB-1R activation on increasing mesolimbic DA activity may provide one explanation for the positive psychotic symptoms induced by D-9-THC (Chen et al, 1990b(Chen et al, , 1991French, 1997;French et al, 1997;Melis et al, 2000;Pistis et al, 2002;Tanda et al, 1997). CB-1R agonists induce cfos in the NAc (Miyamoto et al, 1996) and A10 DA neurons within the ventral tegmentum (Patel and Hillard, 2003), and these effects are blocked by DA D2 receptor antagonists (Miyamoto et al, 1996) and CB-1R antagonists (Patel and Hillard, 2003;Porcella et al, 1998).…”