Leonardo A. Ortega

Naloxone facilitates appetitive extinction and eliminates escape from frustration

Two experiments tested the effects of opioid receptor blockage on behavior. In Experiment 1, rats reinforced for lever pressing with either sucrose or food pellets received treatment with saline, 2, and 10 mg/kg naloxone, i.p. (within-subject design). Naloxone 10 mg/kg increased response latency, but 2 mg/kg had no effect. When shifted to extinction (between-group design), naloxone (2 and 10 mg/kg) facilitated extinction relative to saline animals, after reinforcement with either sucrose or food pellets. In Experiment 2, after 10 sessions of access to 32% sucrose or an empty tube (between-group design), all rats were exposed to the empty tube while allowing them to jump over a barrier into a different compartment. Escape latencies were shorter for downshifted saline than for saline rats always given access to the empty tube. This escape-from-frustration effect was eliminated by naloxone (2 mg/kg, i.p.). Opioid blockage appears to reduce the value of alternative incentives.

Impairment of Recovery From Incentive Downshift After Lesions of the Anterior Cingulate Cortex: Emotional or Cognitive Deficits?

The anterior cinculate cortex (ACC) is known to be implicated in pain-fear and reward expectations. Animals were given electrolytic lesions of the ACC and then trained in the consummatory successive negative contrast (cSNC) situation. In cSNC, animals exposed to an incentive downshift from 32% to 4% sucrose exhibit less consummatory behavior than animals always exposed to 4% sucrose. The ACC lesion had no measurable effects on the consummatory performance of animals before the downshift (i.e., the lesion did not affect consumption of 32% vs. 4% sucrose); on the performance of unshifted, 4% sucrose animals; and on the first downshift trial. However, ACC animals exhibited a significant retardation of recovery from cSNC relative to downshifted shams. Within-trial analysis of consummatory behavior indicated that ACC lesions facilitated cSNC during both the initial and last 100 s of postshift trials after the first downshift experience, relative to sham controls. These results suggest that the ACC is part of the neural circuit normally involved in coping with the emotional response induced by the incentive downshift event by inducing learning of the new incentive conditions.

Memory interfering effects of chlordiazepoxide on consummatory successive negative contrast

Long-Evans rats downshifted from 32% to 4% sucrose solution exhibit lower consummatory behavior during downshift trials than rats exposed only to 4% sucrose. In Experiment 1, this effect, called consummatory successive negative contrast (cSNC), was attenuated by administration of the benzodiazepine anxiolytic chlordiazepoxide (CDP, 5mg/kg, ip) before the second downshift trial (Trial 12), but was not affected when CDP was administered before the first downshift trial (Trial 11). In Experiment 2, CDP administered after Trial 11 actually enhanced the cSNC effect on Trial 12. This posttrial effect of CDP was reduced by delayed administration (Experiment 3). This CDP effect was not present in the absence of incentive downshift (Experiments 4-5), or when animals were tested with the preshift incentive (Experiment 6) or after complete recovery from cSNC (Experiment 7). The posttrial CDP effect was observed after an 8-day interval between Trials 11 and 12 (Experiment 8) and when administered after Trial 12, rather than Trial 11 (Experiment 9). Experiment 10 extended the effect to Wistar rats. Because CDP is a memory interfering drug, it was hypothesized that its posttrial administration interferes with the consolidation of the memory of the downshifted incentive, thus prolonging the mismatch between expected (32% sucrose) and obtained (4% sucrose) incentives that leads to the cSNC effect.

Posttrial d-cycloserine enhances the emotional memory of an incentive downshift event

The present research was designed to determine whether an incentive downshift event induces an emotional memory that can be modulated by d-cycloserine (DCS), a partial agonist at the glycine site of N-methyl-d-aspartate receptor (NMDAR). DCS has been reported to have memory-enhancing properties in other training situations. Experiments 1 and 2 involved a consummatory successive negative contrast (cSNC) situation in which animals are exposed to an incentive downshift involving sucrose solutions of different concentrations. DCS administration (30 mg/kg, ip) immediately after the first 32-to-4% sucrose downshift trial (Experiment 1) retarded recovery of consummatory behavior, but immediately after the first 32-to-6% sucrose downshift trial (Experiment 2) did not affect recovery. There was no evidence that DCS affected consummatory behavior in the absence of an incentive downshift in a manner analogous to a conditioned taste aversion (Experiment 3). These results suggest that activation of NMDARs via the glycine modulatory site enhances the emotional memory triggered by exposure to an incentive downshift event.

Role of the opioid system in incentive downshift situations

Previous research has shown that opioid blockage enhances consummatory successive negative contrast (cSNC)-a suppression of consummatory behavior following a downshift from 32% to 4% sucrose solution. In Experiment 1, administration of the nonselective opioid receptor antagonist naloxone (2 mg/kg, ip) distorted the comparison between expected and received incentives. The results of Experiment 2 discarded the alternative that naloxone enhances cSNC by inducing a conditioned taste aversion. The results of Experiments 3a-3c provided no evidence that opioid administration after the first downshift trial modulated subsequent consummatory performance. The opioids tested included naloxone (2mg/kg, ip), the delta-opioid receptor selective antagonist naltrindole (1 mg/kg, ip), and the delta-opioid receptor selective agonist DPDPE (24 microg/kg, ip). The selected doses have proven in earlier experiments to be effective when administered before training. Experiments 4-5 failed to uncover any effects of posttraining opioid blockage with naloxone in an appetitive extinction task (autoshaping with lever-food pairings). These results add to our previous understanding of opioid function in situations involving incentive downshifts, suggesting a role in the comparison process that triggers cSNC, but no apparent function in memory consolidation related to the downshift event.

Role of the ventrolateral orbital cortex and medial prefrontal cortex in incentive downshift situations

The present research evaluated the role of two prefrontal cortex areas, the ventrolateral orbital cortex (VLO) and the medial prefrontal cortex (mPFC), on two situations involving incentive downshifts, consummatory successive negative contrast (cSNC) with sucrose solutions and Pavlovian autoshaping following continuous vs. partial reinforcement with food pellets. Animals received electrolytic lesions and then were tested on cSNC, autoshaping, open-field activity, and sucrose sensitivity. Lesions of the VLO reduced suppression of consummatory behavior after the incentive downshift, but only during the first downshift trial, and also eliminated the enhancement of anticipatory behavior during partial reinforcement, relative to continuous reinforcement, in autoshaping. There was no evidence of specific effects of mPFC lesions on incentive downshifts. Open-field activity was also reduced by VLO lesions, but only in the central area, whereas mPFC lesions had no observable effects on activity. Animals with mPFC lesions exhibited decreased consumption of the lowest sucrose concentration, whereas no effects were observed in animals with VLO lesions. These results suggest that the VLO may exert nonassociative (i.e., motivational, emotional) influences on behavior in situations involving incentive downshifts. No clear role on incentive downshift was revealed by mPFC lesions.

Reward loss and addiction: Opportunities for cross-pollination

Paradigms used to study the response to and consequences of exposure to reward loss have been underutilized in approaches to the psychobiology of substance use disorders. We propose here that bringing these two areas into contact will help expanding our understanding of both reward loss and addictive behavior, hence opening up opportunities for cross-pollination. This review focuses on two lines of research that point to parallels. First, several neurochemical systems involved in addiction are also involved in the modulation of the behavioral effects of reward loss, including opioid, GABA, and dopamine receptors. Second, there are extensive overlaps in the brain circuitry underlying both reward loss and addiction. Common components of this system include, at least, the amygdala, ventral and dorsal striatum, and various prefrontal cortex regions. Four emerging avenues of research that benefit from emphasis on the common ground between reward loss and addiction are reviewed, namely, the neural circuitry involved in reward devaluation, the influence of genetic and reward history on the behavioral vulnerability and resilience, the role of competing natural rewards, and emotional self-medication. An understanding of the role of reward loss in addiction will point to a deeper understanding of the initiation and maintenance of substance use disorders.

Endogenous Opioids, Opioid Receptors, and Incentive Processes

Opioid receptors and endogenous opioid peptides play a role in a wide variety of behavioral and physiological processes. Four types of opioid receptors have been identified: mu (MOR), delta (DOR), kappa (KOP), and opioid-receptor-like receptor (ORL-1). A variety of endogenous opioids have been identified, including β-endorphin, met-enkephalin, dynorphins, and nociceptin, among others. Whereas endogenous opioids are relatively nonselective, several receptor-selective compounds are available for research purposes (e.g., DAMGO, DPDPE, and U50,488H selectively agonize MOR, DOR, and KOR, respectively). This has permitted researchers to identify the role played by specific opioid receptors in incentive processes. A brief overview of opioid receptors and neuropeptides is followed by a review of recent research on their role in modulating absolute and relative incentive value. Incentive value refers to the hedonic dimension of stimuli such as food and fluids, i.e., to their appetitive or aversive value. Opioid release is involved in two major functions related to incentive value. First, they influence food palatability and so-called liking orofacial responses. Second, they are implicated in the behavioral adjustment to situations involving unexpected incentive devaluations. Opioid function in these situations is surprisingly selective. Thus, for example, different opioid receptors affect behavior at different points in the process of adjustment to reward devaluation.

Extinction of Food-Reinforced Instrumental Behavior in Japanese Quail (Coturnix japonica)

Japanese quail (Coturnix japonica) were reinforced with food for traversing a runway for either 18 or 36 trials, administered at a rate of 1 trial per day. Then, all animals received 18 extinction trials. The latency to run from the start box to the goal box was the dependent variable. Extinction was significantly slower in animals that had received 50% partial reinforcement during acquisition, whether relative to a group matched in terms of acquisition trials (36 trials, twice the number of reinforced trials) or relative to a group matched in terms of reinforcements (18 trials). The latter group was also matched in terms of the temporal distribution of acquisition trials with the partial reinforcement group, being trained only on days when the partial group was scheduled to receive a reinforced trial. Thus, there was evidence of a spaced-trial partial reinforcement extinction effect. A comparison of groups receiving large versus small reward magnitudes yielded no evidence of the spaced-trial magnitude of reinforcement extinction effect, even though the large-reward group consumed approximately 3 times more food than the small-reward group. Moreover, a comparison of groups that received 36 versus 18 acquisition trials produced no evidence of the spaced-trial overtraining extinction effect, even though acquisition latencies were significantly lower for the group that received 36 acquisition trials. These results are discussed in relation to comparative research on learning phenomena involving incentive downshift manipulations.