Abstract
The curve-shift (rate-frequency) paradigm was used to quantify the interaction of cocaine administration with the rewarding effects of lateral hypothalamic electrical stimulation. First, eight animals were tested at 48-h intervals with increasing doses of cocaine (0.5, 1, 2, 4, 8, 16 or 32 mg/kg i.p.); tests with saline were given on intervening days. Cocaine produced dose-orderly leftward shifts of the functions relating response rate to stimulation frequency, which reduced, for each animal, the amount of stimulation required to sustain responding; the two highest doses of the drug shifted the mean rate-frequency curve by 0.47 log units, more than doubling the rewarding potency of the brain stimulation. Baseline thresholds did not change between tests. Next, evidence for sensitization or tolerance was sought from five additional groups of animals, one group given 4 mg/kg and two groups given 16 mg/kg of cocaine at 48-h intervals, and another two groups maintained for 7 days with thrice-daily injections of 10 mg/kg of cocaine or saline. Consistent with results seen in other brain stimulation reward paradigms, there was no evidence of tolerance or sensitization to cocaine’s reward-potentiating effects as quantified in the rate-frequency paradigm.
Footnotes
-
Send reprint requests to: Roy A. Wise, Concordia University, CSBN H-1013, 1455 deMaisonneuve Blvd., West, Montreal, Quebec, Canada H3G 1 M8.
-
↵1 Supported by grants to R.A.W. from National Institute on Drug Abuse (United States) and Fonds pour la Formation de Chercheurs et l’Aide à la Recherche (Québec) and by a predoctoral fellowship (P.B.) from the Medical Research Council of Canada.
-
↵3 Note that the failure suggested in the title ofWasserman et al. (1982) is reflected in only the first few trials of each session. The decay of this “spared” priming effect undergoes a rapid extinction-like process that suggests it is a memory-dependent holdover from prior reinforcement (see Skinner, 1933). The robust component of the priming effect is memory independent (Gallistel et al., 1974) and should thus not undergo extinction; it is absent in the neuroleptic-treated animals of this experiment. Wasserman et al. (1982) did not see a sustained priming effect in neuroleptic-treated animals and Espositoet al. (1979), whose paradigm offers an uncontaminated measure of priming effects, saw neuroleptic-induced loss of stimulation effectiveness. Thus, although there may be a memory-dependent contribution to the priming effect that is not dopamine-dependent for its expression (it almost certainly is dopamine-dependent for its development: Beninger and Hahn, 1983; Beninger and Phillips, 1980), the robust effect of priming is lost in neuroleptic-treated animals.
-
↵2 The term “reward” is used here to reflect the combined effects of reinforcement (of which there are two types) and of “priming” or “incentive motivation” which are usually confounded in these experiments (Wise, 1989). See “Discussion.”
- Received March 27, 1997.
- Accepted August 26, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|