Behavioural and dopaminergic alterations induced by a low dose of WIN 55,212-2 in a conditioned place preference procedure.
OBJECTIVE
This study investigated the role of the cannabinoid CB1 receptor agonist, WIN 55,212-2, on motor activity. Subsequently, the effects of a low, stimulatory dose of WIN 55,212-2 and cocaine, as a positive control, were evaluated using a conditioned place preference (CPP) procedure. Upon completion of CPP, in rats that had been treated with WIN 55,212-2, dopaminergic status and spontaneous and d-amphetamine-induced motor activity were assessed.


METHODS
Sprague-Dawley rats were evaluated for habituated motor activity following WIN 55,212-2 (0, 0.1, 0.3, 1 mg/kg, i.p.) administration. A stimulatory dose of WIN 55,212-2 (0.1 mg/kg, i.p.) and cocaine (20 mg/kg, i.p.) was selected to assess CPP behaviour. Upon completion of CPP, in one group, tissue levels of dopamine and its metabolites were measured in distinct brain regions (dorsal striatum, nucleus accumbens, prefrontal cortex, amygdala, hippocampus) using High Performance Liquid Chromatography with electrochemical detection. In another group, spontaneous and D-amphetamine-induced motor activity was evaluated in an open-field apparatus.


RESULTS
The lowest dose of WIN 55,212-2 increased motor activity but did not produce CPP. As expected, cocaine induced clear CPP. Dopaminergic status was increased in a region-specific way and motor activity was enhanced following a challenge of D-amphetamine in rats that had been administered with WIN 55,212-2 during conditioning.


CONCLUSIONS
A stimulatory effect of WIN 55,212-2 on motor activity was not accompanied by place preference. Upon completion of the CPP procedure, this dose was found to induce region-specific hyperdopaminergia along with a greater sensitivity to a subsequent challenge dose of D-amphetamine.
Polissidis
Alexia
A
Department of Pharmacology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Chouliara
Olga
O
Galanopoulos
Andreas
A
Marselos
Marios
M
Papadopoulou-Daifoti
Zeta
Z
Antoniou
Katerina
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D048588:Benzoxazines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002186:Cannabinoids / Q000819:agonists*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D009949:Orientation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003913:Dextroamphetamine; D004298:Dopamine