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

Abstract

Cannabinoid administration modulates both dopaminergic and glutamatergic neurotransmission. The present study examines the effects of high and low dose WIN55,212-2, a CB1 receptor agonist, on extracellular dopamine and glutamate release in vivo via brain microdialysis in the nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) in parallel to its effects on locomotor activity. WIN55,212-2 increased extracellular dopamine in the NAc (1 mg/kg i.p.), striatum (0.1 and 1 mg/kg i.p.) and PFC (1 mg/kg i.p.). Glutamate release was also elevated by WIN55,212-2 in the PFC (1 mg/kg i.p.) whereas in the NAc (0.1 and 1 mg/kg i.p.) and striatum, it was reduced (1 mg/kg i.p.). WIN55,212-2 administration produced hyperlocomotion at the lower dose (0.1 mg/kg i.p.) and hypolocomotion at the higher dose (1 mg/kg i.p.). Co-administration with the CB1 antagonist, SR-141716A (0.03 mg/kg i.p.), prevented the above effects. According to the present results, WIN55,212-2 affected locomotor activity biphasically while exerting converging effects on dopamine activity but diverging effects on glutamate release between cortical and subcortical regions, especially at the higher dose. These findings emphasize the involvement of the CB1 receptor in the simultaneous modulation of dopaminergic and glutamatergic neurotransmission in brain regions involved in reward and locomotion and suggest possible underlying mechanisms of acute cannabinoid exposure and its psychoactive and behavioural manifestations.

Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats

“…We should note that total motor activity during test days, in both experiments, remained unaffected, which excludes the possibility of an unspecific inhibitory effect in animal activity. Our findings related to CPP acquisition (Chaperon et al, 1998; Yu et al, 2011) and expression, together with our previous findings (Polissidis et al, 2009, 2013), further support and strengthen the concept that pharmacological blockade of CB1 receptors diminishes the motivational value of cocaine. Our data are in line with previous studies showing that CB1 receptor antagonism decreases cocaine-induced reinstatement of cocaine seeking in rodents (De Vries et al, 2001; Xi et al, 2006; Adamczyk et al, 2012) and cue-induced reinstatement of cocaine seeking in rodents and non-human primates (De Vries et al, 2001; Schindler et al, 2016).…”

Effects of glucagon-like peptide-1 receptor stimulation and blockade on food consumption and body weight in rats treated with a cannabinoid CB1 receptor agonist WIN 55,212-2

“…Another possible mechanism by which both agents decreased food consumption is their suppressive effect on locomotor activity. Earlier studies demonstrated that both WIN 55,212-2 and exendin-4 at the doses similar to those used in our study decreased motor activity in animals [37,38]. Thus, the sedative action of both drugs can be responsible for the decrease in appetite.…”

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

“…Several previous studies have demonstrated similar biphasic effects of cannabinoid agonists in different paradigms: low doses of these components usually induce anxiolytic-like effects, while higher doses are anxiogenic or ineffective (Hill and Gorzalka, 2004; Viveros et al, 2005; Fogaca et al, 2012). Moreover, a low dose (0.1 mg/kg) of WIN stimulated motor activity, whereas a higher dose (1 mg/kg) decreased this response (Polissidis et al, 2013). Similarly, in mice submitted to a CFC task, THC exerted biphasic effects on fear-coping strategies, with lower and higher doses favoring active and passive responses, respectively (Metna-Laurent et al, 2012).…”