Prime-, stress-, and cue-induced reinstatement of extinguished drug-reinforced responding in rats: cocaine as the prototypical drug of abuse

Abstract

This unit describes the testing of rats in prime-, footshock-, and cue-induced reinstatement procedures. Evaluating rats in these procedures enables the assessment of treatments on behavior thought to model drug relapse precipitated by re-contact with an abused drug (prime-induced), induced by stress (footshock-induced), or by stimuli previously associated with drug administration (cue-induced). For instance, levels of reinstatement under the effects of test compound administration could be compared to levels under vehicle administration to help identify potential treatments for drug relapse, or reinstatement levels of different rat strains could be compared to identify potential genetic determinants of perseverative drug-seeking behavior. Cocaine is used as a prototypical drug of abuse, and relapse to its use serves as the model in this unit, but other self-administered drugs could readily be substituted with little modification to the procedures.

Figure 1

Catheter introducer components showing unmodified 1 ml syringe and 27 gauge needle above and completed catheter below.

Figure 2

Catheter flush syringe assembly with attached Tygon® tubing. Two catheter-sealing caps are shown in the upper left.

Figure 3

Magnification of the tapered tip of a polyurethane jugular catheter.

Figure 4

Completed tapered polyurethane catheter on gauge card. Also shown is catheter connection post/button as assembled during surgery.

Figure 5

Mean active lever presses during the final session of self-administration and of extinction, and during the cocaine prime-, cue- and footshock-induced reinstatement tests in rats that had previously self-administered cocaine. Brackets through bars indicate SEM. Intragastric injections of vehicle (saline for prime and cue tests, and 0.25% methylcellulose for footshock tests) preceded tests by 30 min. N=12 for all groups.

Figure 6

Figure 6 (upper frame). Mean numbers of active lever presses during the cocaine footshock-induced reinstatement test session as a function of haloperidol dose. Brackets through the bars indicate ±SEM. “VEH” = results of the vehicle-treatment group. Asterisks indicate significantly different (P<0.05) from vehicle. N=12 for each condition. Figure 6 (lower frame). Mean numbers of inactive lever presses during the cocaine prime-induced reinstatement test session as a function of Drug X dose. Other details as in Figure 2A.

Figure 7

Mean active lever presses during cocaine prime-, cue- and footshock-induced reinstatement tests in rats when tested with vehicle or doses (mg/kg i.g.) of JDTic which had previously self-administered cocaine. Brackets through bars indicate SEM. Dotted lines indicate range of mean responses on the last day of extinction. N=12 for all groups.