The rate of intravenous cocaine or amphetamine delivery does not influence drug-taking and drug-seeking behavior in rats

Abstract

We studied the influence of rate of intravenous infusion of cocaine or amphetamine on drug-taking and seeking behavior. First, drug-naive rats were tested for acquisition of self-administration of increasing doses of amphetamine or cocaine infused over 5 or 100 s. Second, self-administration of cocaine or amphetamine infused over 5-100 s was assessed on fixed or progressive-ratio (PR) reinforcement schedules. Finally, the ability of a single 5 or 100 s amphetamine or cocaine infusion to reinstate extinguished drug seeking was assessed. Although slower infusion rates produced a small effect on drug taking under continuous-reinforcement conditions, infusion rate did not alter drug taking on intermittent or PR reinforcement schedules, or the ability of cocaine or amphetamine to reinstate drug seeking. Taken together, our results suggest that variation in drug delivery rate over a range that we previously found alters the induction of behavioral sensitization, gene-expression and striatal dopamine activity, does not markedly alter drug-taking or seeking behavior.

Figure 1

The effect of varying rate of infusion (5 or 100 sec) on cocaine (n=10 and 9 for the 5 and 100 sec conditions, respectively) or amphetamine (n=10 and 8 for the 5 and 100 sec conditions, respectively) intake (number of infusions) across 20 self-administration sessions. Rats responded on an FR1 schedule or reinforcement for increasing doses of cocaine (0.5, 0.6, and 0.7 mg/kg/inf) or amphetamine (0.2, 0.25 and 0.3 mg/kg/inf), each infusion delivered over 5 sec (open symbols) or 100 sec (closed symbols). Stippled lines separate different dose/stages of the experiment.

Figure 2

Dose-effect curves for the effect of varying rate of infusion (5 or 100 sec) on the acquisition of cocaine (n=10 and 9 for the 5 and 100 sec conditions, respectively) or amphetamine (n=10 and 8 for the 5 and 100 sec conditions, respectively) self-administration across increasing doses of cocaine (0.5, 0.6, and 0.7 mg/kg/inf) or amphetamine (0.2, 0.25 and 0.3 mg/kg/inf). Panels a and c show the number of infusions earned and panels b and d the number of responses into the drug reinforced (circles) and non-reinforced (triangles) nose poke ports. Asterisks indicate significant differences between the 5 and 100 sec infusion conditions (p < 0.05). Rate of infusion did not affect acquisition of cocaine taking and amphetamine self-administration was increased for rats earning self-infusions delivered over 100 sec versus 5 sec.

Figure 3

The effects of varying rate of infusion (5, 25, 50 and 100 sec infusion duration) on responding for cocaine of amphetamine maintained on different FR schedules of reinforcement. After acquisition of stable responding for 0.4 mg/kg/inf cocaine or 0.2 mg/kg/inf amphetamine, each rat was tested on 4 consecutive sessions with each of 4 infusion rates (in random order) for responding on, first an FR1 schedule (n=15 and 19 for the cocaine and amphetamine conditions, respectively), and subsequently on an FR2 (cocaine; n=13) or FR5 (amphetamine; n = 14) schedule. Asterisks’ indicate significant differences between the 5 and 100 sec infusion conditions (p < 0.05). Contrary to expectations, both cocaine and amphetamine intake decreased, by 20% and 21%, respectively, when infused over 100 sec versus 5 sec and no effects were evident on responding maintained on higher order schedules of drug reinforcement. At the same time responding into the cocaine or amphetamine reinforced nose-poke manipulandum significantly increases during the 100 sec infusion/time-out period (this effect only approached significance in rats responding for cocaine on an FR2 schedule).

Figure 4

The effects of varying rate of infusion (5, 25, 50 and 100 sec infusion duration) on progressive ratio (PR) schedule responding for cocaine (panels a and b; n=10) or amphetamine (panels c and d; n=13). Once stable PR responding for established for 0.4 and then 0.8 mg/kg/inf cocaine or 0.1 and then 0.2 mg/kg/inf amphetamine, each rat was tested on 4 consecutive sessions with each of 4 infusion rates in random order. In both the cocaine and amphetamine groups, infusion rate did not significantly affect the number of infusions or responses into the active or inactive ports.

Figure 5

The effects of varying rate of infusion (5 or 50/100 sec infusion duration) on amphetamine (n=7, 4 and 5 for the 5, 50 and 100 sec conditions, respectively) or cocaine-priming (n=8, 5 and 5 for the 5, 50 and 100 sec conditions, respectively) induced reinstatement of extinguished drug seeking. Data from the 50 and 100 sec conditions were pooled to yield a single group (50–100 sec) for comparison. A single i.v. infusion or cocaine (2.0 mg/kg) or amphetamine (1.0 mg/kg) triggered robust reinstatement relative to post-extinction levels of responding (average response during last 3 extinction sessions). Swords indicate a significant difference in responding between extinction and reinstatement test sessions. Rate of infusion did not affect the magnitude of cocaine or amphetamine-priming induced reinstatement.