Individual differences in the effects of cannabinoids on motor activity, dopaminergic activity and DARPP-32 phosphorylation in distinct regions of the brain

Abstract

This study explored the behavioural, neurochemical and molecular effects of Delta9-tetrahydrocannabinol (Delta9-THC) and WIN55,212-2, in two rat phenotypes, distinguished on the basis of their vertical activity upon exposure to a novel environment, as high responders (HR) and low responders (LR). Motor effects were assessed under habituated vs. non-habituated conditions. Dopaminergic activity and DARPP-32 phosphorylation were measured in the dorsal striatum, nucleus accumbens, prefrontal cortex and amygdala. These cannabinoids influenced motor activity in a biphasic manner, i.e. low doses stimulated, whereas high doses suppressed motor activity. Dopamine (DA) biosynthesis was increased in most brain regions studied following Delta9-THC administration mainly in HR rats, and low-dose WIN55,212-2 increased DA biosynthesis in HR rats only. Both high and low doses of Delta9-THC increased DARPP-32 phosphorylation in most brain regions studied in both phenotypes, an effect that was also observed following high-dose WIN55,212-2 administration only in the striatum. The present results provide further support for a key role of cannabinoids in the regulation of motoric responses and elements of dopaminergic neurotransmission and reveal their complex differential effects in distinct rat phenotypes, as seen with other drugs of abuse.

The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate release region dependently

“…The present results are in line with previous findings that have shown dosedependent increases in dopamine efflux in the PFC following D 9 -THC administration (Chen et al 1990a ;Pistis et al 2002). In support of these results, our previous findings have shown that both D 9 -THC and WIN55,212-2 stimulate dopamine biosynthesis in the PFC (Polissidis et al , 2010 ; an effect that was also observed by Jentsch et al (1997) after D 9 -THC administration. Both D 9 -THC and WIN55,212-2 have been observed to stimulate mesoprefrontal dopaminergic neurotransmission and, in both cases, SR-141716A effectively reversed this result (Diana et al 1998).…”

“…In line with our previous findings, WIN55,212-2 modified motor activity biphasically (Polissidis et al 2010). Specifically, a low dose (0.1 mg/kg) WIN55,212-2 stimulated locomotor activity and a high dose of WIN55,212-2 (1 mg/kg) decreased locomotor activity.…”

“…Increases in extracellular dopamine release in the NAc have also been reported after D 9 -THC and WIN55,212-2 administration (Chen et al 1990b ;Fadda et al 2006 ;Lecca et al 2006 ;Ng Cheong Ton et al 1988 ;Tanda et al 1997). According to our previous data, both D 9 -THC and WIN55,212-2 stimulate dopamine biosynthesis in these brain regions (Polissidis et al , 2010. The low dose of WIN55,212-2 tested was unable to increase accumbal dopamine, although there was a tendency at later time-points.…”

“…Consistently, pharmacological treatments with CB 1 agonists exert biphasic effects, especially concerning motor activity, with low doses inducing motor activation and high doses producing suppressed motor activity or catalepsy (Drews et al 2005 ;Polissidis et al 2010 ;Rodvelt et al 2007 ;Sanudo-Pena et al 2000 ;Sulcova et al 1998). Interestingly, no study has focused on the simultaneous in vivo estimation of glutamate and dopamine in distinct brain regions after specific doses of cannabinoids, which produce excitation or suppression of motor activity, respectively.…”

“…In addition, dose-dependent increases in dopamine efflux have been observed in the striatum and the PFC (Chen et al 1990a ;Malone & Taylor, 1999). In this regard, neurochemical studies assessing the release of dopamine following cannabinoid exposure fundamentally support a correlation between cannabinoid-induced behavioural effects and dopamine alterations in distinct brain regions (Polissidis et al , 2010.…”