There has long been need for a behavioural intervention that attenuates cue-evoked drug-seeking, but the optimal method remains obscure. To address this, we report three approaches to extinguish cue-evoked drug-seeking measured in a Pavlovian to instrumental transfer design, in non-treatment seeking adult smokers and alcohol drinkers. The results showed that the ability of a drug stimulus to transfer control over a separately trained drug-seeking response was not affected by the stimulus undergoing Pavlovian extinction training in experiment 1, but was abolished by the stimulus undergoing discriminative extinction training in experiment 2, and was abolished by explicit verbal instructions stating that the stimulus did not signal a more effective response-drug contingency in experiment 3. These data suggest that cue-evoked drug-seeking is mediated by a propositional hierarchical instrumental expectancy that the drug-seeking response is more likely to be rewarded in that stimulus. Methods which degraded this hierarchical expectancy were effective in the laboratory, and so may have therapeutic potential.

BackgroundTwo theories explain how negative mood primes smoking behaviour. The stimulus–response (S-R) account argues that in the negative mood state, smoking is experienced as more reinforcing, establishing a direct (automatic) association between the negative mood state and smoking behaviour. By contrast, the incentive learning account argues that in the negative mood state smoking is expected to be more reinforcing, which integrates with instrumental knowledge of the response required to produce that outcome.ObjectivesOne differential prediction is that whereas the incentive learning account anticipates that negative mood induction could augment a novel tobacco-seeking response in an extinction test, the S-R account could not explain this effect because the extinction test prevents S-R learning by omitting experience of the reinforcer.MethodsTo test this, overnight-deprived daily smokers (n = 44) acquired two instrumental responses for tobacco and chocolate points, respectively, before smoking to satiety. Half then received negative mood induction to raise the expected value of tobacco, opposing satiety, whilst the remainder received positive mood induction. Finally, a choice between tobacco and chocolate was measured in extinction to test whether negative mood could augment tobacco choice, opposing satiety, in the absence of direct experience of tobacco reinforcement.ResultsNegative mood induction not only abolished the devaluation of tobacco choice, but participants with a significant increase in negative mood increased their tobacco choice in extinction, despite satiety.ConclusionsThese findings suggest that negative mood augments drug-seeking by raising the expected value of the drug through incentive learning, rather than through automatic S-R control.

Extinction of the discriminative stimulus effects of drugs has received little research attention. Using a one-lever foodreinforcement (VI-1 min) operant procedure with rats (N = 16), the studies reported here assessed extinction, spontaneous recovery, and reinstatement of responding to the discriminative stimulus effects of nicotine. Experiment 1 found evidence for retention of differential responding to IP administrations of nicotine after a 3-month (87 days) delay following acquisition. Experiment 2 compared spontaneous recovery of discriminative control 2 and 4 weeks following extinction. Additionally, the impact of noncontingent reinforcement on discriminative control was evaluated (reinstatemen~. During extinction training, nicotine (.4 mg/kg) or saline was administered 15 min prior to each 15-min session, as they were during training, but responding was not reinforced under either stimulus condition. Spontaneous recovery (SR) of responding under the SD condition occurred during a session (11 th) preceded by two consecutive S'" sessions. Matched by response rate, 8 rats were randomly assigned to either a 2-week delay group or a 4-week delay group. There was no evidence for SR of discriminated responding to the drugs 2 or 4 weeks following the final extinction session. Between-group comparisons further revealed that SR did not vary as a function of delay following extinction. Reinstatement of stimulus control was observed following 2 brief sessions of noncontingent food delivery (levers retracted and conducted in the absence of the drug cues). These results suggest that the maintenance and extinction of the discriminative stimulus effects of nicotine are temporally stable. Theoretical ideas regarding drug self-administration, craving, and therapy are entertained.

A within-subject design was used to characterize the effects of dose manipulations on discriminative and self-reported effects of oral diazepam and buspirone. Subjects were trained to discriminate diazepam (10 mg) versus placebo (n = 10), or buspirone (10 or 15 mg) versus placebo (n = 9). The compounds were identified to subjects by letter code before discrimination training began. In later sessions, correct identifications at 2 hr after the oral administration of drug earned money. All subjects showed accurate discrimination performance during the test-of-acquisition phase. In a low-dose generalization phase, diazepam and buspirone produced dose-related increases in drug identifications across a four-fold range of doses. In a subsequent low-dose training phase, in which subjects were trained to discriminate progressively lower drug doses, the median lowest discriminable dose of diazepam and buspirone was 2.5 and 7.5 mg, respectively. Dose-response functions for drug identifications were shifted leftward in the low-dose training phase relative to the low-dose generalization phase, suggesting that reinforcement of progressively lower doses enhances drug discriminability. The self-reported effects of diazepam and buspirone were similar (e.g., both drugs increased ratings of drug strength and clumsy/uncoordinated) and different (e.g., diazepam but not buspirone increased ratings of drowsy/sleepy; buspirone but not diazepam increased ratings of tense/nervous). This study demonstrates discriminative and self-reported effects of diazepam and buspirone at doses lower than previously shown to be behaviorally active, and suggests that at commonly used clinical doses, diazepam is relatively more discriminable than buspirone.