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alpha(2A)-Adrenoceptors regulate d-amphetamine-induced hyperactivity and behavioural sensitization in mice
Juuso Juhila1, Aapo Honkanen, Jukka Sallinen
1Department of Pharmacology and Clinical Pharmacology, University of Turku, FI-20520 Turku, Finland. juuso.juhila@helsinki.fi
European Journal of Pharmacology
|June 28, 2005
Summary
Alpha-2A adrenoceptor knockout mice show altered responses to d-amphetamine, impacting locomotor activation and sensitization. Blocking alpha-2A adrenoceptors may reduce drug sensitization and motor side effects.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Stimulants like d-amphetamine increase dopamine release in the central nervous system (CNS), causing locomotor activation.
- Repeated stimulant administration leads to behavioral sensitization, potentially linked to addiction and dependence.
- Noradrenergic mechanisms also play a role in psychostimulant effects.
Purpose of the Study:
- To investigate the role of alpha-2A adrenoceptor subtype A (alpha(2A)-AR) in d-amphetamine-induced locomotor effects and sensitization.
- To determine if alpha(2A)-AR antagonism can modulate these effects.
Main Methods:
- Comparison of locomotor activity in alpha(2A)-AR knockout (KO) mice and wild-type (WT) controls following acute and repeated d-amphetamine administration.
- Assessment of sensitization development and expression using pretreatment with the alpha(2)-adrenoceptor antagonist atipamezole.
- Evaluation of persistent sensitization after a 2-week abstinence period.
- Measurement of d-amphetamine's rewarding properties via conditioned place preference.
Main Results:
- Alpha(2A)-AR KO mice exhibited supersensitivity to acute d-amphetamine's locomotor effects.
- Both genotypes developed locomotor sensitization, but it was less pronounced in alpha(2A)-AR KO mice.
- Atipamezole reduced hyperactivation development and attenuated sensitization expression, particularly in WT mice.
- Alpha(2A)-AR KO mice did not show persistent sensitization after abstinence.
- Rewarding properties of d-amphetamine were comparable between genotypes.
Conclusions:
- Alpha-2 adrenoceptors, specifically the alpha(2A) subtype, control d-amphetamine-induced acute and sensitized locomotor effects.
- Alpha(2A)-AR antagonism may offer a strategy to mitigate drug sensitization and motor complications associated with dopaminergic agents.
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