Hippocampal lesions in rats produce both a retrograde and an anterograde amnesia of contextual fear conditioning. The present experiments examined the anterograde deficit in context conditioning. The deficit produced by electrolytic hippocampal lesions was apparent when training occurred on 7, 14, or 28 days following surgery, confirming the durability of the amnesia. The role of the hippocampus in context conditioning may be related to an NMDA (N-methyl-D-aspartate) receptor-mediated process. Both NMDA hippocampal lesions and intrahippocampal administration of an NMDA antagonist produced anterograde amnesia. Animals preexposed to the conditioning context 28 days prior to hippocampal lesioning were protected from the deficit normally produced by the lesions. Thus, the hippocampus must form a contextual representation during preexposure that is subsequently stored elsewhere. Once formed this representation of the context can be associated with an unconditional stimulus.

This study investigated the increase in expression in the amygdala of 2 immediate-early genes, c-fos and NGFI-A, following contextual fear conditioning. The immediate-shock freezing deficit paradigm was used to compare rats that received footshock after exploring a context to rats that received footshock immediately after placement in the chamber. The former procedure produces contextual fear conditioning while the latter does not. Rats were either handled (handled group), placed in a test chamber without receiving footshock (context-no-footshock group), received footshock immediately upon being placed in the chamber (immediate-footshock group), or received footshock after a 1 min delay (delayed-footshock group). Only the delayed-footshock group displayed a fear response (freezing behavior). Rats were sacrificed either 15 min after the experience or after a retention test 24 h later. The c-fos mRNA was increased in the medial nucleus of the amygdala in all of the groups that were placed in the test chamber. However, rats that received footshock (immediate- and delayed-footshock groups) had greater levels of c-fos mRNA expression than rats of the context-no-footshock group. The c-fos mRNA expression in the immediate- and delayed-footshock groups did not differ. However, after the retention test, the expression of c-fos mRNA in the medial nucleus of the amygdala did not differ between groups. In contrast to c-fos, NGFI-A mRNA expression in the lateral nucleus of the amygdala was greater in the delayed-footshock group than the handled and context-no-footshock groups 15 min after the footshock. This elevation in NGFI-A mRNA was not seen in the immediate-footshock group. This suggests that NGFI-A mRNA in the lateral nucleus of the amygdala may play a role in contextual fear conditioning.

Conditional stimuli (CS) associated with painful unconditional stimuli (US) produce a naloxone-reversible analgesia. The analgesia serves as a negative-feedback regulation of fear conditioning that can account for the impact of US intensity and CS predictiveness on Pavlovian fear conditioning. In Experiment 1 training under naloxone produced learning curves that approached the same high asymptote despite US intensity. Shifting drug treatment during acquisition had effects that paralleled US intensity shifts. In Experiment 3 naloxone reversed Hall-Pearce (1979) negative transfer using a contextual CS, indicating that conditional analgesia acquired during the CS-weak-footshock phase retards acquisition in the CS-strong-footshock phase. Experiment 5 used a tone CS in both a latent-inhibition and a negative-transfer procedure. Only negative transfer was blocked by naloxone. Therefore, negative transfer but not latent inhibition is mediated by a reduction of US processing.

Massed presentation of unsignaled shock results in less conditional freezing to contextual cues than do distributed presentations. Consistent with an account of the learning deficit based on the perceptual-defensive-recuperative theory, the massed-shock deficit was attenuated by preexposure to shock or the conditioning context. This formulation was also successfully applied to the deficit in conditioning that occurs when a single shock is given immediately after placement in a context. Opponent-process theory was not supported by 2 findings: (a) The deficit was neither enhanced by shock preexposure nor reduced by an opioid antagonist, and (b) unconditional reactions were greater with massed shock. Inconsistent with the suggestion that the effect is a performance artifact specific to freezing, the massed-shock deficit was apparent for a 2nd measure of conditioning.

Pretreatment with opioid antagonists enhances acquisition of Pavlovian fear conditioning. The present experiments attempted to characterize the type of opioid receptor responsible for this effect using a procedure that assessed the fear of rats to a chamber previously associated with electric shock (1 mA, 0.75 s). Freezing, a species-typical immobility, was employed as an index of fear. Two mu opioid antagonists, CTOP (40 ng) and naloxonazine (10 micrograms), enhanced conditioning. On the other hand, the kappa antagonist nor-binaltorphimine reduced conditioning. Two delta antagonist treatments (16-methyl cyprenorphine and naltrindole) had no reliable effect on acquisition. Thus the enhancement of conditioning appears to be mediated by mu receptors. Previous research has shown that the conditional fear produced by these procedures caused an analgesia that is also mediated by mu receptors. It is argued that the enhancement effect occurs because of an antagonism of this analgesia and that the analgesia normally acts to regulate the level of fear conditioning.