Pretreatment with the dopamine agonist 7-OH-DPAT shifts the cocaine self-administration dose-effect function to the left under different schedules in the rat.
This study tested the hypothesis that administration of the dopamine agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) shifts the cocaine self-administration dose-effect function to the left, rather than producing nonspecific effects or exclusively enhancing the rate-decreasing effects of high doses of cocaine. Under fixed-ratio or progressive-ratio schedules, rats were allowed to intravenously self-administer cocaine, 7-OH-DPAT, or a combination of cocaine and 7-OH-DPAT. In additional tests under fixed-ratio schedules, cocaine self-administration followed subcutaneous pretreatment with 7-OH-DPAT. Cocaine dose-effect functions were obtained by varying the unit dose of cocaine either between test sessions or within a single session. Intravenous 7-OH-DPAT (1-4µg) decreased self-administration of the training dose of cocaine (0.25mg) under a fixed-ratio schedule, but failed to shift the entire cocaine self-administration dose-effect function to the left under fixed-ratio or progressive-ratio schedules. 7-OH-DPAT alone maintained i.v. self-administration under these schedules, but produced a shallow self-administration dose-effect function, relative to cocaine, under the progressive-ratio schedule. In contrast to intravenous 7-OH-DPAT, s.c. pretreatment with 7-OH-DPAT (0.1-0.4mg/kg) not only decreased self-administration of the training dose of cocaine but also lowered the minimum effective dose of cocaine under fixed-ratio schedules, producing a shift to the left of the cocaine self-administration dose-effect function; these effects were independent of whether the dose of cocaine was varied between sessions or within a single session. Likewise under a multiple schedule, in which responding was maintained by cocaine and food in alternate components, s.c. pretreatment with 7-OH-DPAT increased self-administration of the dose of cocaine on the ascending limb of the dose-effect function and decreased self-administration of doses of cocaine on the descending limb, while uniformly decreasing responding for food. These observations suggest that pretreatment with 7-OH-DPAT enhances the reinforcing properties of cocaine rather than producing nonspecific effects or enhancing exclusively the rate-decreasing effects of high doses of self-administered cocaine.
Caine
S.B.
SB
Department of Neuropharmacology, The Scripps Research Institute, CVN-7 La Jolla, CA 92037, USA.
Koob
G.F.
GF