Conditioned inhibition of cyclophosphamide-induced taste aversion

Rats in an experimental group received trials during which 1 flavor (saccharin) was always followed by cyclophosphamide, an immunosuppressive drug, but another (vanilla) was not. An unconditioned stimulus-only group served as a control. Flavor-preference tests revealed that conditioned excitation and conditioned inhibition occurred in the conditioned group subjects but not in the control group subjects. This demonstration suggests that a conditioned inhibitor might be used to modify conditioned and unconditioned immune system functions, for example, natural killer-cell activity.     

Conditioned suppression of counting behavior in rats

Three rats were trained on a schedule in which a response on lever B was reinforced only if it was preceded by a minimum number of consecutive responses on lever A. The minimum requirement was 27 A responses for Rat 1, and 20 A responses for Rats 2 and 3. The schedule maintained high rates of responding on lever A, and a slow, spaced pattern of responding on lever B. The mean number of consecutive responses on lever A was slightly greater than the minimum required. The effect of superimposing on this behavior a stimulus that ended with an unavoidable shock was the suppression of responding on both levers during the pre-shock stimulus. Responses on lever A were more suppressed, and the proportion of relatively short response runs on lever A during the pre-shock stimulus increased. With all three rats, the mean number of consecutive responses on lever A during the pre-shock stimulus decreased to a value below the minimum requirement for reinforcement of the subsequent B response.     

Conditioned inhibition from incomplete reductions in the probability of reinforcement

Five experiments, all using appetitive, discrete trial operant conditioning, studied the properties of a stimulus that signalled a reduction in the probability of reward. Discriminations were trained in which reinforcement was available on 100% of trials signalled by a tone, but only on some occasions when the tone was presented simultaneously with a light. The properties of the light were assessed in summation tests with a clicker. The first two experiments established that if the tone-light compound signalled reinforcement on only 25%, 33% or 50% of trials the light acted as a discriminative inhibitor, suppressing responding maintained by the clicker. In these experiments reinforcement had been available on 86.7% of clicker trials during initial training. Experiments 3, 4 and 5 examined further the properties of the light after animals had been trained on a discrimination where reinforcement was available on 50% of trials signalled by the tone-light compound. The light was evaluated in a summation test with a clicker, which had signalled only a 25% or 15% probability of a reinforcement. In this instance, the light did not suppress the responding maintained by the clicker. Instead, the light acted as an excitatory discriminative stimulus to enhance that responding. This dependence of the properties of the light on the reinforcement history of the clicker poses problems for most contemporary models of inhibitory performance.     

Conditioned inhibition of craving in drug addiction: A pilot experiment

It seems likely that an important reason for the limited success of aversion treatment of drug addiction has been that the aversion is applied only to extrinsic stimuli associated with the drug. No attempt is ordinarily made to combat the endogenous habit.

In the present experiment a subject with a Demerol (Pethidine) addiction of 3 years' standing was instructed to give himself a severe shock from a portable apparatus whenever he felt a desire for the drug arise endogenously. On three occasions he gave himself 4, 3 and 2 shocks respectively, dispelling the craving. After this the apparatus broke down, but for a period of 12 weeks the patient remained free from any but minor cravings that he could easily control.     

Extinction-induced neuroplasticity attenuates stress-induced cocaine seeking: a state-dependent learning hypothesis

Chronic drug use weakens excitatory neocortical input to the nucleus accumbens (NAc). We previously reported that extinction training, a form of inhibitory learning that progressively reduces cocaine-seeking behaviour when reward is withheld, reverses this deficit by up-regulating GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptors in the NAc. The level of GluR1 up-regulation is positively associated with a reduction in cocaine seeking, suggesting that extinction-induced up-regulation in AMPA receptors in the NAc opposes motivational influences that maintain cocaine seeking. This hypothesis is supported by the finding that over-expression of GluR1 and GluR2 in the NAc facilitates extinction of cocaine self-administration. Furthermore, a single extinction training session conducted during GluR1 and GluR2 over-expression strongly and selectively attenuates the ability of an environmental stressor to trigger relapse to cocaine seeking long after GluR1 and GluR2 over-expression declines. These results could suggest that excitatory input to the NAc promotes extinction learning, but only when memory is recalled under stressful situations. Recent studies indicate that both environmental stress and the frustrative stress of withholding reward during extinction of drug self-administration induce similar neurochemical events in the NAc. These neurochemical events could impose a "state-dependency" on extinction learning such that subsequent exposure to stress acts as a cue to enhance retrieval of extinction memory. Our results suggest that extinction-induced up-regulation in NAc AMPA receptors acts reciprocally to facilitate state-dependent extinction learning, as stressful situations evoke extinction memories that exert powerful inhibitory control over drug-seeking behaviour. These results may have important therapeutic implications for behaviour-based approaches aimed at treating drug addiction.     

Fixed-interval schedules of intravenous cocaine presentation in rats

Fixed-interval schedules of intravenous cocaine presentation were examined as a function of injection dose (0.32 to 0.64 mg/kg) and interval duration (200 to 400 sec) in two rats. Cocaine was found to exert a dose-related temporal control over the initiation of responding that was unaffected by the fixed-interval contingency. Fixed-interval pause duration was linearly related to injection dose and was the same duration as the interresponse time found on continuous reinforcement schedules of cocaine presentation. The fixed-interval pause remained constant with changes in interval duration. Characteristic fixed-interval patterns of responding were observed. However, overall response rates were inversely related to injection dose and directly related to interval duration. Running response rates varied unsystematically with both variables. These findings are at variance with results typically found in studies of fixed-interval food and electric shock presentation.     

Conditioned inhibition of fear: Evidence for a competing response mechanism

In two experiments, inhibitory conditioning was attempted by presenting a discrete CS in a neutral stimulus environment shortly following the termination of either shock (Experiment 1) or a second discrete CS which had been paired in a forward manner with shock (Experiment 2). Evidence of successful inhibitory conditioning was mixed in Experiment 1, where the properties of the CS were assessed within an escape-from-fear procedure. Postresponse presentations of the CS enhanced performance, whereas the presentation of the CS prior to responding did not have the expected degrading effect on performance. In Experiment 2, the inhibitory properties of the CS were assessed by combining this stimulus with an excitatory CS and presenting the compound to rats engaged in a water-reinforced licking response. Less response suppression was found in reaction to this compound relative to three separate comparison conditions, thus witnessing the success of the inhibitory-conditioning procedure used. The common assumption that inhibitory conditioning results from the nonreinforcement of a CS in a situation where reinforcement is expected, i.e., one which contains previously reinforced cues, is not supported by these data, for no previously reinforced cues were simultaneously presented with the CS during inhibitory training. The data are in agreement with a conditioned antagonistic-response interpretation of inhibitory conditioning.     

Learning about cues that prevent an outcome: Conditioned inhibition and differential inhibition in human predictive learning

Summation tests were used to assess whether participants in a human predictive judgement task learned that some cues (foods) prevented the occurrence of the outcome (migraine). In three experiments the preventative effect of a conditioned inhibitor, I, trained in the design, P+, PI-, I-, was stronger than that of a negative control cue, N, that had been presented alone with the same frequency and simply predicted no outcome. This control cue, N, also passed the summation test when compared to a novel control cue. Experiments 2 and 3 examined whether the latter negative control effect was attributable to differential inhibition. Manipulations designed to alter context learning and the magnitude of the negative contingency did not affect the properties of the negative control cue. Thus, these experiments did not support the possibility that a cue given simple negative training acquires differential inhibition. Regardless of the mechanism underlying the negative control effect, the consistent finding that the conditioned inhibition cue, I, reduced prediction of the outcome more than did the negative control cue, N, provides evidence for true conditioned inhibition whose acquisition requires co-occurrence of the preventative cue with a positive training cue.     

Conditioned aversions and their memories in 5-day-old rats during suckling

Association learning during suckling was investigated. Five-day-old rats equipped with tongue cannulae placed either 2 mm rostral or 4-6 mm caudal to the intermolar eminence received sweet or salty solutions while suckling. This ingestion was followed by lithium chloride toxicosis. Pups with anterior cannulae took in considerably less fluid than control pups when tested 5 or 16 days later. A series of control groups demonstrated that this acquired aversion was associative in nature. Pups with posterior cannulae did not form the association. The failure of 5-day-old rats with posterior cannulae to form associations while suckling is not due to the prevention of conditioning by the act of suckling per se. Rather, the failure rests in the fluid's not reaching anterior taste receptors when injected into the posterior oropharynx, where the nipple normally empties its contents. These findings are discussed in terms of the transfer of information obtained during suckling prior to weaning, to feeding and drinking during and after weaning.