Effects of Cannabinoids on Dopamine Release in the Corpus Striatum and the Nucleus Accumbens In Vitro

Abstract

Cannabinoid receptors are widely distributed in the nuclei of the extrapyramidal motor and mesolimbic reward systems; their exact functions are, however, not known. The aim of the present study was to characterize the effects of cannabinoids on the electrically evoked release of endogenous dopamine in the corpus striatum and the nucleus accumbens. In rat brain slices dopamine release elicited by single electrical pulses was determined by fast cyclic voltammetry. Dopamine release was markedly inhibited by the OP 2 opioid receptor agonist U-50488 and the D 2 /D 3 dopamine receptor agonist quinpirole, indicating that our method is suitable for studying presynaptic modulation of dopamine release. In contrast, the CB 1 /CB 2 cannabinoid receptor agonists WIN55212-2 (10 Ϫ6 M) and CP55940 (10 Ϫ6 -10 Ϫ5 M) and the CB 1 cannabinoid receptor antagonist SR141716A (10 Ϫ6 M) had no effect on the electrically evoked dopamine release in the corpus striatum and the nucleus accumbens. The lack of a presynaptic effect on terminals of nigrostriatal and mesolimbic dopaminergic neurons is in accord with the anatomical distribution of cannabinoid receptors: The perikarya of these neurons in the substantia nigra and the ventral tegmental area do not synthesize mRNA, and hence protein, for CB 1 and CB 2 cannabinoid receptors. It is therefore unlikely that presynaptic modulation of dopamine release in the corpus striatum and the nucleus accumbens plays a role in the extrapyramidal motor and rewarding effects of cannabinoids. Key Words: Cannabinoid receptor-Corpus striatumDopamine release-Nucleus accumbens-Presynaptic receptor-Voltammetry. J. Neurochem. 73, 1084Neurochem. 73, -1089Neurochem. 73, (1999.The primary molecular targets of the active components of marijuana and hashish are the cannabinoid receptors. Two G protein-coupled receptors have been identified, the CB 1 and CB 2 cannabinoid receptors; the CB 1 receptor is preferentially located on neurons, whereas the CB 2 receptor occurs mainly on peripheral nonneuronal cells (for review, see Howlett, 1995;Compton et al., 1996;Pertwee, 1997).The distribution of cannabinoid receptors in the CNS is well characterized (Herkenham et al., 1991;Jansen et al., 1992;Mailleux and Vanderhaeghen, 1992;Romero et al., 1997;Tsou et al., 1998). Moderate to high concentrations were observed in practically all regions belonging to the extrapyramidal motor system, e.g., corpus striatum, substantia nigra, globus pallidus, entopeduncular nucleus, and subthalamic nucleus, and the mesolimbic reward system, e.g., nucleus accumbens and ventral tegmental area. Accordingly, cannabinoids can markedly affect the function of these systems, producing catalepsy and rewarding effects (Howlett, 1995;Compton et al., 1996;Tanda et al., 1997;Martellotta et al., 1998). The exact mechanisms of these effects-how functions of identified neurons of the extrapyramidal motor and mesolimbic reward systems are influenced-are not known.It was recently reported that cannabinoids inhibit the electrically evoked releas...

Cannabinoids Enhance Subsecond Dopamine Release in the Nucleus Accumbens of Awake Rats

“…Indeed, they are unlikely to be mediated in the NAc because cannabinoids applied directly to dopaminergic terminals in NAc brain slices do not affect evoked dopamine release (Szabo et al, 1999); however, cannabinoids do produce an increase in the overall firing rate of dopaminergic neurons in the VTA (French, 1997;French et al, 1997;Cheer et al, 2000aCheer et al, , 2003Szabo et al, 2002). An augmentation in the burst-firing rate of dopaminergic neurons could increase the amplitude of transient dopamine release because, when neurons shift to a bursting pattern, the resulting action potentials cause greater extrasynaptic levels of transmitter compared with the same number of equally spaced action potentials at a lower frequency (Gonon and Buda, 1985;Gonon, 1988;Wightman et al, 1988).…”

Involvement of Cannabinoid Receptors in the Regulation of Neurotransmitter Release in the Rodent Striatum: A Combined Immunochemical and Pharmacological Analysis

“…Cannabinoids, applied in vivo, increase striatal dopaminergic transmission (Malone and Taylor, 1999;Melis et al, 2000), likely via increasing the neuronal firing in the ventral tegmental area (Robbe et al, 2001) and in the substantia nigra. However, in vitro, they directly did not affect the release of dopamine (Szabo et al, 1999). Cannabinoids depress both GABAergic (Szabo et al, 1998) and glutamatergic [caudate-putamen (Gerdeman and Lovinger, 2001;Huang et al, 2001;Gerdeman et al, 2002;Brown et al, 2003;Ronesi et al, 2004), nucleus accumbens (Robbe et al, 2001(Robbe et al, , 2002] synaptic currents through presynaptic CB 1 receptor activation.…”

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

“…Dopamine release in rat nucleus accumbens has been shown to increase after administration of exogenous cannabinoids (Tanda et al, 1997;Szabo et al, 1999). Activation of D2-like dopamine receptors, but not D1-like receptors, increased anandamide release in dorsal striatum (Giuffrida et al, 1999).…”