Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency.
This study examines whether behavioural sensitization to the dopamine agonist, quinpirole, reflects an increase in the drug's potency and/or efficacy to induce locomotion, and how these parameters are influenced by environmental context. Three experiments were conducted in which animals received either chronic quinpirole (10 x 0.5 mg/kg, twice weekly) or saline injections in either the home cage environment, an alternate environment or the testing environment (activity monitors), followed by a dose-response test for the expression of sensitization in the activity monitors. Compared to the acute dose-response relationship, chronic quinpirole increased the maximum response. This increase in efficacy was significantly higher in animals treated with quinpirole in a non-home cage environment compared to those that received chronic treatment in the home cage. A leftward shift in the dose-effect function was observed only in animals with prior drug experience in the testing environment. Results indicate that locomotor sensitization to quinpirole reflects an environment-modulated increase in the drug's efficacy, and an environment-dependent increase in drug potency. Efficacy and potency may be subject to sensitization by non-associational and associational mechanisms, respectively.
Szumlinski
K K
KK
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Allan
M
M
Talangbayan
H
H
Tracey
A
A
Szechtman
H
H
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004777:Environment; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats
D018491:Dopamine Agonists; D019257:Quinpirole