Time-dependent effects of prazosin on the development of methamphetamine conditioned hyperactivity and context-specific sensitization in mice.
The present experiments examined the effects of prazosin, a selective α₁-adrenergic receptor antagonist, on the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Mice received an injection of vehicle (distilled water) or prazosin (0.5, 1.0 or 2.0 mg/kg) 30 min prior to a second injection of vehicle (saline) or methamphetamine (1.0 mg/kg) during the conditioning sessions (Experiment 1). Following the conditioning sessions, mice were tested for conditioned hyperactivity and then tested for context-specific sensitization. In subsequent experiments, mice received an injection of vehicle (distilled water) or prazosin (2.0 mg/kg) immediately (Experiment 2) or 24 h (Experiment 3) after the conditioning sessions and then tested for conditioned hyperactivity and context-specific sensitization. Prazosin dose-dependently blocked the development of methamphetamine conditioned hyperactivity and context-specific sensitization when administered prior to the methamphetamine during the conditioning phase; however nonspecific motor impairments also were observed (Experiment 1). Immediate (Experiment 2), but not the 24-h delay (Experiment 3), post-session administration of prazosin attenuated the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Nonspecific motor impairments were not observed in these latter experiments. Collectively, these results suggest that the α₁-adrenergic receptor mediates the development of methamphetamine-conditioned hyperactivity and context-specific sensitization, perhaps by altering memory consolidation and/or reconsolidation processes.
Dickinson College, USA. Electronic address: aowhite@uci.edu.
André O
AO
White
Dickinson College, USA. Electronic address: rauhuta@dickinson.edu.
Anthony S
AS
Rauhut
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D017109:Akathisia, Drug-Induced / Q000188:drug therapy*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D011224:Prazosin
Antagonist; Conditioning; Memory consolidation; Methamphetamine; Sensitization; α(1)-Adrenergic receptor