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Dose–Effect Functions for Cocaine Self-Administration: Effects of Schedule and Dosing Procedure

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Abstract

Research related to determining how procedural variables can alter dose–effect functions for cocaine self-administration is limited. Toward clarifying the role of procedural variables, responding was maintained in rats under either variable-interval (VI) or fixed-ratio (FR) schedules of cocaine infusion. In addition to free-operant FR schedules, discrete-trial FR schedules were evaluated. The dose–effect functions were obtained by either substituting a dose for the usual daily dose, instituting a particular dose for several sessions, or making all doses available within a session. Dose–effect functions for response rate (or number of trials with infusions for the discrete-trial FR) were bitonic for the VI and discrete-trial FR schedules but tended to be strictly decreasing for the free-operant FR schedules. Responding was maintained under FR schedules by a low dose (0.083 mg/infusion) if the dose was substituted for a higher daily dose but not when made available daily. Rate of response was higher under ratio schedules at 0.17 mg/infusion when this dose occurred within the context of other higher doses within a session than when the dose was simply substituted for a higher daily dose. These data indicate that procedural variables can alter dose–response curves for cocaine self-administration.

Section snippets

Subjects

Twenty-seven male Fischer rats, approximately 90–120 days old at the beginning of the experiments, served as subjects. Each subject was individually housed and had access to water ad lib. Subjects were typically meal-deprived during training (see Procedure) but were given access to food ad lib after responding was well established.

Apparatus

Although some specific characteristics of the operant chambers used in each experiment were slightly different, the chambers were all roughly the same size and did

Results

Fig. 1 shows response rate (left panel) and rate of drug intake (right panel) as a function of dose for Experiments 1, 2, and 4 (free-operant FRs and VI) averaged across subjects. Over the range of doses tested, response rate was an inverse function of dose under both free-operant FR procedures and was a bitonic function under the VI schedule. Dose was a statistically significant variable (one-way repeated-measures ANOVA) within each procedure type: VI [F(4, 126) = 37.186, p < 0.0001],

Discussion

Cocaine self-administration was examined by using a variety of procedures that generated dose–effect functions that differed in certain respects. The most striking difference among the dose–effect functions concerned the dose at which the highest rate of responding (or largest number of trials with infusions, in the discrete-trial procedure) occurred. In the probe portion of Experiment 5, this dose was, for four of five rats, 0.083 mg/infusion (Fig. 5). Under the VI schedule, however, the peak

Acknowledgements

This research was supported by National Institute on Drug Abuse grants DA 07246, DA 06634, and DA 03628.

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