Effect of naloxone on conditioned suppression in rats.

Effects of agonists and antagonists at the GABA/benzodiazepine receptor on conditioned suppression in rats

Three experiments were conducted to examine the effect of assessment procedure, either conditioned punishment extinction or conditioned suppression reacquisition, on the associative outcome of backward conditioning in the rat. Each experiment consisted of three phases: (a) magazine and barpress training; (b) Pavlovian training in which groups received one of backward, explicitly unpaired, or no presentation of a conditioned stimulus (CS) and unconditioned stimulus (US); and (c) either conditioned punishment or conditioned suppression transfer of training tests. In Experiment 1, backward conditioning resulted in excitatory associative effects during the conditioned punishment test. In Experiment 2, backward conditioning produced excitatory conditioning when assessed by a conditioned suppression reacquisition test. In Experiment 3, a number of backward conditioning parameters were manipulated, and backward pairings yielded facilitative reacquisition relative to the unpaired group, but did not differ from the no-treatment control group. The pattern of results suggests that backward conditioning produces qualitatively similar outcomes when assessed by a conditioned punishment extinction or conditioned suppression reacquisition test.

Loss of control by a less valid or by a less salient stimulus compounded with a better predictor of reinforcement

We utilized a potent, selective, and orally‐bio‐available antagonist with documented engagement with nociceptin receptors (NOP) to assess antidepressant‐ and anxioltyic‐related effects of blockade of NOP receptors. The NOP receptor antagonist, Cpd 1, displayed antidepressant‐like neurochemical and behavioral effects in rats and mice. Serotonin outflow in rat prefrontal cortex was enhanced without affecting norepinephrine or dopamine. Correspondingly Cpd 1 decreased immobility in the forced swim test (FST). Cpd 1 augmented the effects of fluoxetine without changing target occupancies of either drug. Anti‐immobility effects of Cpd 1 were absent in mice without NOP receptors. Cpd 1 also produced anxiolytic‐like effects in some rodent models: decreased stimulus‐elicited freezing in mice and decreased stress‐induced hyperthermia in rats. Cdp 1 was not active in: marble‐burying in mice, novelty‐suppressed feeding in mice, conditioned suppression in rats, punished food‐maintained responding in rats, and the 4‐plate test in mice. Cpd 1 did not disrupte performance in 5‐choice serial reaction time tests or delayed matching‐to‐position in rats. Cpd 1 was mildly wake promoting in rats. These data suggest that Cpd 1 has unique antidepressant‐ and anxiolytic‐related pharmacological effects in rodents.

Treatments that attenuate latent inhibition (LI) were examined using conditioned suppression in rats. In Experiment 1, retarded conditioned responding was produced by nonreinforced exposure to the CS prior to the CS-US pairings used to assess retardation (i.e., conventional LI). In Experiment la, retarded conditioned responding was induced by preexposure to pairings of the CS and a weak US prior to retardation-test pairings of the CS with a strong US (i.e., Hall-Pearce [1979] LI). Both types of LI were attenuated by extensive exposure to the training context (i.e., context extinction) following the CS-US pairings of the retardation test. Experiment 2 examined the specificity of the attenuated LI effect observed in Experiment 1. After preexposure to two different CSs in two different contexts, each CS was paired with a US in its respective preexposure context. One of the two contexts was then extinguished. This attenuated LI to a greater degree for the CS that had been trained in the extinguished context. Experiment 3 differentiated the roles in LI of CS-context associations and context-US associations. Following preexposure to the CS in the training context, LI was reduced by further exposure to the CS outside the training context. This observation was interpreted as implicating the CS-context association as a factor in LI. Thus, the results of these experiments suggest that LI is a performance deficit mediated by unusually strong CS-context associations. Implications for Wagner’s (1981) SOP model and Miller and Matzel’s (1988) comparator hypothesis are discussed.

Removing the bar in an appetitive lever-press task, the effects of number of CS-US pairings (1, 2, or 4), modality of the CS (2 tones vs light and tone) and prior CS habituation trials on the development of discriminated conditioned suppression were evaluated. Two or 4 CS-US pairings produced virtually a perfect discrimination with complete suppression to CS and little suppression to CS−. In addition there was a significant interaction of modality × shock, indicating that going from CS+ to CS− had far less effect when the stimuli were in the same modality (T-T) than when modality changed (L-T). The effect of habituation training on suppression while not significant was in the expected direction, attenuating suppression to both CS+ and CS−.

The effects of naloxone and picrotoxin on the sedative and anticonflict effects of benzodiazepines