Free-Operant Avoidance Behavior by Rats after Reinforcer Revaluation Using Opioid Agonists and d-Amphetamine

Abstract

The associative processes that support free-operant instrumental avoidance behavior are still unknown. We used a revaluation procedure to determine whether the performance of an avoidance response is sensitive to the current value of the aversive, negative reinforcer. Rats were trained on an unsignaled, free-operant lever press avoidance paradigm in which each response avoided or escaped shock and produced a 5 s feedback stimulus. The revaluation procedure consisted of noncontingent presentations of the shock in the absence of the lever either paired or unpaired with systemic morphine and in a different cohort with systemic D-amphetamine. Rats were then tested drug free during an extinction test. In both the D-amphetamine and morphine groups, pairing of the drug and shock decreased subsequent avoidance responding during the extinction test, suggesting that avoidance behavior was sensitive to the current incentive value of the aversive negative reinforcer. Experiment 2 used central infusions of D-Ala 2 , NMe-Phe 4 , Gly-ol 5 ]-enkephalin (DAMGO), a mu-opioid receptor agonist, in the periacqueductal gray and nucleus accumbens shell to revalue the shock. Infusions of DAMGO in both regions replicated the effects seen with systemic morphine. These results are the first to demonstrate the impact of revaluation of an aversive reinforcer on avoidance behavior using pharmacological agents, thereby providing potential therapeutic targets for the treatment of avoidance behavior symptomatic of anxiety disorders.

Safety signals as instrumental reinforcers during free-operant avoidance

“…The effect of safety signal revaluation observed in Experiment 4 contrasts with our recent observation (Fernando et al 2014) following revaluation of the primary negative reinforcer, the footshock, rather than the safety signal. After training on the same avoidance schedule as used in Experiment 4, we gave noncontingent exposure to the footshock under morphine before testing drug-free avoidance performance in an extinction test without shocks.…”

“…The free-operant avoidance behavior trained in this study has two potential sources of reinforcement: (1) negative reinforcement arising from the negative contingency between the aversive footshock and the avoidance response and (2) positive reinforcement engendered by the positive contingency between the safety signal and avoidance response. Recently, we (Fernando et al 2014) found that the negative reinforcer, footshock, can be revalued by presenting footshocks in the absence of the lever, when the rats are under the influence of morphine, d-amphetamine or central infusions of the m-opioid agonist DAMGO (paired conditions). We therefore adopted an analogous procedure to revalue the safety signal, reasoning that due to the involvement of the opioid system in enhancing the hedonic impact of rewarding stimuli (Berridge 2003), this revaluation treatment should increase the value of the safety signal.…”

Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance

“…However, note that in our task this remains speculation, since our current data set does not allow us to prove that our rats were acting habitually in response to all three trial type cues. Recent work has shown that rats well-trained on avoidance paradigms still show sensitivity to the devaluation of the shock outcome, which suggests that they remain goal-directed with respect to this action–outcome contingency41. This could suggest, then, that the NAc is monitoring predictions but does not directly initiate action in this task unless there are changes in action-outcome contingencies.…”

Exaggerated Acquisition and Resistance to Extinction of Avoidance Behavior in Treated Heroin-Dependent Men

“…14 One type of addiction that has been extensively studied in animals, including in the context of avoidance behavior, is opioid addiction. 5–7, 15–24 While reports often showed increased avoidance behavior in rodents that were given opioids, 15–19 this was not always the case. 20–22, 24 …”

“…In rodents, opioid receptors in the midbrain have been shown to regulate extinction of aversive conditioning, 25 opioid agonists decreased avoidance during extinction of free-operant avoidance, 24 and opiate seeking behavior is extinguished slowly, with a high risk of relapse. 26 Indeed, evidence suggests that rodents with history of opioid use tend to respond to drug cues even when drugs are absent.…”