Effects of the cannabinoid receptor ligands on anxiety-related effects of d-amphetamine and nicotine in the mouse elevated plus maze test.
The purpose of the experiments was to examine the anxiety-related effects of d-amphetamine and nicotine, and the possible involvement of the endocannabinoid system. D-amphetamine (2 mg/kg, ip) was administered acutely or daily for 8 days. On the 9th day, mice were challenged with d-amphetamine (2 mg/kg, ip) or nicotine (0.1 mg/kg, sc), and were tested in the elevated plus maze. Additionally, a distinct group of mice was pretreated with an acute (0.1 mg/kg,sc) or subchronic nicotine (6 days), and subjected to nicotine (0.1 mg/kg, sc) or d-amphetamine (2 mg/kg, ip) challenge on the 7th day. The cannabinoid receptor ligands, WIN 55,212-2, a non-selective cannabinoid receptor agonist (0.25; 0.5 and 1 mg/kg, ip) and rimonabant, a CB1 cannabinoid receptor antagonist (0.25; 0.5; 1 and 2 mg/kg, ip) were injected prior to each injection of saline or acute and subchronic d-amphetamine or nicotine. We observed that acute anxiogenic and subchronic anxiolytic effects of both psychostimulants as well as the development of full cross-tolerance to their anxiogenic effects were dose-dependently blunted by ineffective doses of WIN 55,212-2 (0.25 and 0.5 mg/kg) and rimonabant (0.5 and 1 mg/kg). These results provide evidence that the endogenous cannabinoid system is involved in the anxiety-related responses to d-amphetamine and/or nicotine.
Biala
G
G
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland. grazyna.biala@umlub.pl
Kruk
M
M
Budzynska
B
B
D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000523:psychology*; D048588:Benzoxazines / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000502:physiology; D000077285:Rimonabant
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D000697:Central Nervous System Stimulants; D008024:Ligands; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043882:Receptors, Cannabinoid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009538:Nicotine; D000077285:Rimonabant; D003913:Dextroamphetamine