Effects of Compounding Drug‐related Stimuli: Escalation of Heroin Self‐administration

Abstract

Previous experiments have demonstrated that presenting independently established discriminative stimuli in compound can substantially increase operant responding maintained by food reinforcement or shock avoidance. Recently, this phenomenon was also shown to occur with cocaine self-administration. The present study further assessed the generality of these stimulus-compounding effects by systematically replicating them with heroin self-administration. Rats' nose-poke responses produced intravenous heroin (0.025 mg/kg per infusion) on a variable-ratio schedule when either a tone or a light was present. In the absence of these stimuli, responding was not reinforced. Once discriminative control by the tone and light had been established, the stimuli were presented in compound under extinction (with heroin discontinued) or maintenance conditions (with heroin available during test-stimulus presentations). In extinction, the tone-light compound increased responding approximately threefold compared to tone or light alone. Under maintenance conditions, compounding increased heroin intake approximately twofold. These effects closely matched those obtained earlier with cocaine. This consistency across pharmacological classes and across drug and nondrug reinforcers further confirms that (a) self-administered drugs support conditioning and learning in a manner similar to that supported by other reinforcers; and (b) multiple drug-related cues interact in lawful and predictable ways to affect drug seeking and consumption.

Effect of drug-paired exteroceptive stimulus presentations on methamphetamine reinstatement in rats

“…In reinstatement studies drug-paired stimuli are often presented during acquisition, extinction and reinstatement. These stimuli have been shown to facilitate acquisition and enhance maintenance levels of self-administration (Caggiula et al 2002, Deroche-Gamonet et al 2002, Panlilio et al 2000. In a series of two cocaine reinstatement papers from our laboratory, one using non-contingent cocaine primes and a second using footshock stress, we found that statistically significant reinstatement behavior did not occur when cues, which had been present during self-administration, were omitted during extinction and reinstatement testing Beardsley 2005, Shelton et al 2004).…”

Pavlovian Extinction of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats Varies as a Function of Context

“…Rescorla (2006) has shown that when two excitatory CS+s are placed in compound, the total excitatory strength doubles. For example, using either a cocaine or heroin self-administration procedure, Panlilio, Schindler, and Weiss (1996), and later Panlilio, Weiss, and Schindler (2000), demonstrated that when two separately established S D 's were compounded, response rates doubled during extinction. However, as Rescorla (2006) also showed, if the stimuli are continually nonreinforced, extinction progresses more rapidly, thus promoting little recovery of responding.…”

A stimulus-control account of regulated drug intake in rats

“…It is well established that the interoceptive discriminative-stimulus properties of drugs can control operant responding maintained by non-drug reinforcers in rats (Colpaert 1999) and that exteroceptive discriminative stimuli such as a cue light can exert precise control over drug selfadministration responding (Panlilio et al 1996(Panlilio et al , 2000bWeiss et al 2003). Therefore, it is reasonable to expect that interoceptive effects of self-administered drugs can control the selfadministration response.…”