Cannabinoid self-administration increases dopamine release in the nucleus accumbens

Abstract

In the present study, dopamine release was monitored during cannabinoid self-administration in rats to achieve a detailed understanding of the way in which dopamine mediates the reinforcing effects of cannabinoids. Extracellular dopamine levels were measured in the shell of the nucleus accumbens of either Lister Hooded or Long Evans rats trained to self-administer the cannabinoid CB1 receptor agonist WIN 55,212-2. A significant relationship between extracellular dopamine levels and bar-pressing rates was observed in both strains, as the dopamine content appreciably increased in respect to basal values during cannabinoid intake. Importantly, dopamine was not modified when trained rats were shifted to vehicle self-administration suggesting that an enhanced activity of the mesolimbic dopamine pathway underlies cannabinoid-taking behaviour.

Neurobiological mechanisms of cannabinoid addiction

“…Few years ago, by combining intravenous self-administration procedure with in vivo microdialysis technique we measured fluctuations of DA levels in the NAc of rats during voluntary WIN 55,212-2 intake (Fadda et al, 2006). In this study we demonstrated that self-administered doses of intravenous WIN 55,212-2 increase DA release to a similar extent in the NAc shell of Lister Hooded and Long…”

“…At preclinical level, it has been now definitely established that cannabinoids act on the brain in a way similar to other drugs of abuse (Gardner, 2002), producing clear subjective effects and leading to drug-seeking and drug-taking behavior (Martellotta et al, 1998;Fattore et al, 2001Fattore et al, , 2007bJustinova et al, 2003Justinova et al, , 2005Spano et al, 2004;Fadda et al, 2006;Deiana et al, 2007). However, the eCB system is not only the primary site of action for the motivational and reinforcing properties of cannabinoids, but it also exerts an overall modulatory effect on brain reward pathways, thus participating in the addictive properties of most drugs of abuse, such as alcohol (Mechoulam and Parker, 2003), nicotine (Viveros et al, 2006;Forget et al, 2006), cocaine (Arnold, 2005), opioids (Navarro et al, 2001;Fattore et al, 2004Fattore et al, , 2005aFattore et al, , 2007dSpano et al, 2007), methamphetamine (MDMA) (Parrott, 2006), and salvinorin (Braida et al, 2007a,b).…”

“…Thus, intravenous SA of THC and AEA has been demonstrated in squirrel monkeys (Justinova et al, 2003(Justinova et al, , 2005, intravenous SA of WIN 55,212-2 has been reported in drug-naive mice (Martellotta et al, 1998;Ledent et al, 1999;Fattore et al, 2002) and trained rats (Fattore et al, , 2007bSpano et al, 2004;Fadda et al, 2006;Deiana et al, 2007), while intracerebroventricular SA of CP 55,940 has been described in rats (Braida et al, 2001). Interestingly, cannabinoid SA is…”

“…Evans rats, with a significant relationship between extracellular DA levels and bar-pressing rates, thus providing a reasonable neurochemical basis for the reinforcing effects of cannabinoid (Fadda et al, 2006).…”

“…Both THC and synthetic CB1-R agonists dose-dependently enhance firing rate and bursting activity of DA neurons in the VTA, whereas their actions on DA neurons in the pars compacta of the substantia nigra (SNc) are less pronounced. Enhanced electrical activity translates into an increase in DA release in terminal regions, such as the NAc (Cheer et al, 2004;Fadda et al, 2006;Tanda et al, 1997;Pistis et al, 2002b) and the PFC (Chen et al, 1990, Chen et al, 1993Pistis et al, 2002a). Under this aspect, cannabinoids display effects largely similar to those of other drugs of abuse belonging to different classes.…”