The alpha2-adrenoceptor antagonist atipamezole reduces the development and expression of d-amphetamine-induced behavioural sensitization.
Naunyn Schmiedebergs Arch Pharmacol
; 367(3): 274-80, 2003 Mar.
Article
en En
| MEDLINE
| ID: mdl-12644900
ABSTRACT
The possible effect of atipamezole, a potent and specific alpha(2)-adrenoceptor antagonist, on the development and expression of d-amphetamine-induced behavioural sensitization was evaluated in mice. Male (C57Bl/6J) mice were given daily doses of d-amphetamine (2 mg/kg). In addition, groups of mice received injections of atipamezole (0.3 or 1 mg/kg) 20 min before d-amphetamine or vehicle administration. Idazoxan (1 mg/kg) was used in some experiments to extend the results to other alpha(2)-adrenoceptor antagonists. Challenge doses of d-amphetamine were administered to the mice on days 7-9 to evaluate the effects of alpha(2)-adrenoceptor antagonists on the d-amphetamine sensitization, evidenced by increased locomotor activation. Mice treated repeatedly with d-amphetamine developed strong locomotor sensitization that was reduced by pretreatment with alpha(2)-adrenoceptor antagonists. Acute atipamezole at both doses attenuated the expression of d-amphetamine-induced sensitization. Atipamezole at 1 mg/kg alone had no effect on locomotor activity, but the lower dose (0.3 mg/kg) increased locomotor activity after repeated administration. These results indicate that alpha(2)-adrenoceptor antagonists modulate the actions of d-amphetamine in a manner not explicable by their enhancing actions on noradrenaline and dopamine release, and may thus provide a novel approach to the treatment of motor complications caused by dopaminergic agents, such as dyskinesias, and perhaps also drug dependence.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Conducta Animal
/
Dextroanfetamina
/
Antagonistas de Receptores Adrenérgicos alfa 2
/
Imidazoles
Límite:
Animals
Idioma:
En
Revista:
Naunyn Schmiedebergs Arch Pharmacol
Año:
2003
Tipo del documento:
Article
País de afiliación:
Finlandia