title: Cannabinoids negatively modulate striatal glutamate and dopamine release and behavioural output of acute D-amphetamine.
abstract: The cannabinoid system plays a regulatory role in neurotransmission and is involved in the central actions of psychostimulants. This complex interaction between the cannabinoid system and psychostimulants represents a potential pharmacological target for psychosis and addiction. However, most studies have focused on cocaine, therefore, it is unclear whether these findings can be extended to other psychostimulants such as the amphetamines. The present study investigated the effects of WIN55,212-2, a synthetic cannabinoid and SR141716A, a CB1 receptor antagonist, on D-amphetamine-induced locomotor activity and extracellular dopamine and glutamate release in the striatum. Rats were either observed for locomotor activity or glutamate and dopamine neurotransmitter release in the striatum using in vivo microdialysis following intraperitoneal co-administration of D-amphetamine with WIN55,212-2 or SR141716A. Our results demonstrated that d-amphetamine per se induced hyperlocomotion and enhanced dopamine and glutamate release, as expected. WIN55,212-2 dampened these effects when co-administered with d-amphetamine, while alone it displayed its characteristic biphasic motor profile coupled with increases in dopamine and decreases in glutamate release. SR141716A at high doses reduced D-amphetamine-induced hyperlocomotion and completely reversed enhanced dopamine and glutamate release but alone had no effect. These findings validate the capacity of the cannabinoid system to modulate amphetamine-induced behaviour and its neurochemical output, in a state-dependent manner, providing insight into aspects of the neurobiological substrate that underlies amphetamines' psychotogenic and addictive properties.
authors.affiliation: Department of Pharmacology, Medical School, University of Ioannina, Ioannina 45110, Greece; Department of Pharmacology, Medical School, University of Athens, Athens 11527, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Polissidis
authors.affiliation: Department of Pharmacology, Medical School, University of Ioannina, Ioannina 45110, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Chouliara
authors.affiliation: Department of Pharmacology, Medical School, University of Ioannina, Ioannina 45110, Greece; Department of Pharmacology, Medical School, University of Athens, Athens 11527, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Galanopoulos
authors.affiliation: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Athens 11635, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Naxakis
authors.affiliation: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Athens 11635, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Papahatjis
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Athens 11527, Greece.
authors.forename: Z
authors.initials: Z
authors.lastname: Papadopoulou-Daifoti
authors.affiliation: Department of Pharmacology, Medical School, University of Ioannina, Ioannina 45110, Greece. Electronic address: kantoniu@cc.uoi.gr.
authors.forename: K
authors.initials: K
authors.lastname: Antoniou
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000032:analysis*; D004359:Drug Therapy, Combination; D018698:Glutamic Acid / Q000032:analysis*; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D048588:Benzoxazines; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D000697:Central Nervous System Stimulants; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000661:Amphetamine; D000077285:Rimonabant; D004298:Dopamine
keywords: Cannabinoid; Dopamine; Glutamate; Motor activity; d-amphetamine