@article{3061255, title = "The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate release region dependently", author = "Polissidis, A. and Galanopoulos, A. and Naxakis, G. and Papahatjis, D. and Papadopoulou-Daifoti, Z. and Antoniou, K.", journal = "The International Journal of Neuropsychopharmacology", year = "2013", volume = "16", number = "2", pages = "393-403", issn = "1461-1457, 1469-5111", doi = "10.1017/S1461145712000156", keywords = "2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo[1,2,3 de][1,4]benzoxazine; cannabinoid 1 receptor; dopamine; glutamic acid; rimonabant; benzoxazine derivative; cannabinoid receptor agonist; cannabinoid receptor antagonist; dopamine; glutamic acid; morpholine derivative; naphthalene derivative; piperidine derivative; pyrazole derivative, amino acid transport; animal experiment; article; controlled study; corpus striatum; dopamine release; extracellular space; in vivo study; locomotion; male; microdialysis; motor activity; neuromodulation; neurotransmission; nonhuman; nucleus accumbens; prefrontal cortex; priority journal; rat; analysis of variance; animal; brain; dose response; drug effect; histology; metabolism; Sprague Dawley rat; time, Analysis of Variance; Animals; Benzoxazines; Brain; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Dopamine; Dose-Response Relationship, Drug; Glutamic Acid; Male; Microdialysis; Morpholines; Motor Activity; Naphthalenes; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Time Factors", 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 (1Â mg/kg i.p.), striatum (0.1 and 1Â mg/kg i.p.) and PFC (1Â mg/kg i.p.). Glutamate release was also elevated by WIN55,212-2 in the PFC (1Â mg/kg i.p.) whereas in the NAc (0.1 and 1Â mg/kg i.p.) and striatum, it was reduced (1Â mg/kg i.p.). WIN55,212-2 administration produced hyperlocomotion at the lower dose (0.1Â mg/kg i.p.) and hypolocomotion at the higher dose (1Â mg/kg i.p.). Co-Administration with the CB1 antagonist, SR-141716A (0.03Â 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. © CINP 2012." }