Nicotinic acetylcholine receptors of the ventral tegmental area are involved in mediating morphine-state-dependent learning

In the present study, the possible role of nicotinic acetylcholine (nACh) receptors of the ventral tegmental area (VTA) on morphine-state-dependent learning was studied in adult male Wistar rats. As a model of memory, a step-through type passive avoidance task was used. All animals were bilaterally implanted with chronic cannulae in the VTA, trained using a 1 mA foot shock, and tested 24 h after training to measure step-through latency. Post-training subcutaneous (s.c.) injection of morphine (0.5–5 mg/kg) dose-dependently reduced the step-through latency, showing morphine-induced amnesia. Amnesia induced by post-training morphine was significantly reversed by pre-test administration of morphine (2.5–5 mg/kg, s.c.) and induced morphine-state-dependent learning. Pre-test injection of nicotine (0.25–1 μg/rat) into the VTA plus an ineffective dose of morphine (0.5 mg/kg) significantly restored the memory retrieval. It should be noted that pre-test intra-VTA injection of the same doses of nicotine (0.25–1 μg/rat) alone cannot affect memory retention. Furthermore, pre-test intra-VTA injection of the nicotinic acetylcholine receptor antagonist, mecamylamine (1–3 μg/rat) 5 min before the administration of morphine (5 mg/kg, s.c.) dose-dependently inhibited morphine-state-dependent learning. Pre-test injection of the higher dose of mecamylamine (3 μg/rat) into the VTA by itself decreased the step-through latency and induced amnesia. On the other hand, mecamylamine (0.5 and 1 μg/rat, intra-VTA) reversed the effect of nicotine on morphine response. The results indicate that nACh receptors in the VTA participate in the modulation of morphine-induced recovery of memory, on the test day.     

Microinfusion of the D1 receptor antagonist, SCH23390 into the IL but not the BLA impairs consolidation of extinction of auditory fear conditioning

In auditory fear conditioning, repeated presentation of the tone in the absence of the shock leads to extinction of the acquired fear response. Both the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) are involved in extinction. Here we examined this involvement by antagonizing D1 receptors in both regions, in the rat. We microinfused the D1 receptor antagonist, SCH23390, into the infra-limbic part of the mPFC (IL) or BLA at different time points. SCH23390 mircoinfused into the IL either before extinction acquisition or following short extinction training resulted in impairment of extinction consolidation. Microinfusion of SCH23390 into the BLA, prior to acquisition of extinction caused impairment in acquisition of extinction without affecting extinction consolidation. This is supported by the results showing that microinfusion of SCH23390 into the BLA following a short-training session did not affect consolidation. These results further strengthen the role of mPFC in consolidation of extinction while highlighting the role of the D1 receptors in this process.     

Delay-dependent involvement of the rat entorhinal cortex in habituation to a novel environment

Evidence has accumulated that the entorhinal cortex (EC) is involved in memory operations underlying formation of a long-term memory. Because entorhinal-lesioned rats are impaired for long delays in delayed matching and non-matching to sample tasks, it has been proposed that EC contributes to the maintenance of information in short-term memory. In the present study, we asked whether such a time-limited role applies also when learning complex spatial information in a novel environment. We therefore examined the effects of EC lesions on habituation in an object exploration task in which a delay of either 4 min or 10 min is imposed between successive sessions. EC-lesioned rats exhibited a deficit in habituation at 10 min but not 4 min delays. Following habituation, reactions to spatial change (object configuration) and non-spatial change (novel object) were also examined. EC-lesioned rats were impaired in detecting the spatial change but were able to detect a non-spatial change, irrespective of the delay. Overall, the results suggest that EC is involved in maintaining a large amount of novel, multidimensional information in short-term memory therefore enabling formation of long-term memory. Switching to a novelty detection mode would then allow the animal to rapidly adapt to environmental changes. In this mode, EC would preferentially process spatial information rather than non-spatial information.     

Do serotonin1–7 receptors modulate short and long-term memory?

Evidence from invertebrates to human studies indicates that serotonin (5-hydroxytryptamine; 5-HT) system modulates short- (STM) and long-term memory (LTM). This work is primarily focused on analyzing the contribution of 5-HT, cholinergic and glutamatergic receptors as well as protein synthesis to STM and LTM of an autoshaping learning task. It was observed that the inhibition of hippocampal protein synthesis or new mRNA did not produce a significant effect on autoshaping STM performance but it did impair LTM. Both non-contingent protein inhibition and 5-HT depletion showed no effects. It was basically the non-selective 5-HT receptor antagonist cyproheptadine, which facilitated STM. However, the blockade of glutamatergic and cholinergic transmission impaired STM. In contrast, the selective 5-HT(1B) receptor antagonist SB-224289 facilitated both STM and LTM. Selective receptor antagonists for the 5-HT(1A) (WAY100635), 5-HT(1D) (GR127935), 5-HT(2A) (MDL100907), 5-HT(2C/2B) (SB-200646), 5-HT(3) (ondansetron) or 5-HT(4) (GR125487), 5-HT(6) (Ro 04-6790, SB-399885 and SB-35713) or 5-HT(7) (SB-269970) did not impact STM. Nevertheless, WAY100635, MDL100907, SB-200646, GR125487, Ro 04-6790, SB-399885 or SB-357134 facilitated LTM. Notably, some of these changes shown to be independent of food-intake. Concomitantly, these data indicate that '5-HT tone via 5-HT(1B) receptors' might function in a serial manner from STM to LTM, whereas working in parallel using 5-HT(1A), 5-HT(2A), 5-HT(2B/2C), 5-HT(4), or 5-HT(6) receptors.     

Configural learning without reinforcement: Integrated memories for correlates of what,where, and when

In 2 experiments we examined the ability of rats to form configural memories of what auditory stimulus (X or Y) was presented where (Context A or B) and when (morning or afternoon). In both experiments, rats received morning presentations of X in Context A and Y in Context B and afternoon presentations of X in B and Y in A. Subsequently, at midday the rats were exposed to trials where X was paired with footshock whereas Y was not. We then assessed the degree of contextual fear in A and B in the morning and the afternoon. In the morning, rats showed more fear in A than in B, and in the afternoon they showed more fear in B than in A. These results indicate that rats can form configural memories that represent what (X or Y) was presented, where (A or B), and when (morning or afternoon).     

Rats learn to eat more to avoid hunger

Several recent experiments have provided evidence that the ingestion of a distinctive food by rats can be a learnt instrumental act as well as an associatively conditioned reaction. In the previous work, maintenance food was withheld for shorter and longer durations on different days following access to the training food. Extra eating before the longer fast was interpreted as avoidance of hunger. This interpretation was based on the evidence showing that extra eating as a result of classical conditioning comes from pairing food stimuli with the presence of little or no hunger because of repletion with energy nutrients. The theory that the extra eating arose from a response-depletion contingency was tested in the present experiment by training rats on only a long fast or only a short fast. Greater increase in intake was seen before the longer fast. The results also replicated previously seen cycles of increase, decrease, and renewed increase in putative deficit-avoidant eating over about three trials, indicating that the extra eating reduces the response-reinforcing hunger and that the consequent part-extinction restores reinforcement. The shape of the learning curve was consistent with these cycles occurring from the start of training, further supporting the view that the increase in food intake before a long delay in refeeding is hunger-reinforced instrumental behaviour.     

Rats’ memory for time and relational responding in the duration-comparison procedure

Rats were trained in a duration-comparison task to press one lever if the comparison duration (c) was 1.2-s shorter than a standard duration (s), and another lever if c was 1.2-s longer than s. The interval between s and c duration was 1 s. The 10 duration pairs used during training controlled for the absolute duration of c and the total duration of an s-c pair. The total duration of an s-c pair was not predictive of the correct response. In Experiment 1, during equal-duration pair test trials, rats increasingly responded long (i.e., c > s) as the s-c delay was lengthened. In Experiment 2, long responding increased as the s-c delay was lengthened, even when the illumination condition during the s-c delay differed from that during the intertrial interval (ITI). In Experiment 3, transfer to novel duration pairs was assessed. Overall accuracy for the novel duration pairs was significantly above chance, but transfer performance was also affected by the absolute value of the novel c durations. This is the first study to demonstrate that rats can acquire relational duration discriminations. As in previous studies with pigeons the evidence was consistent with subjective-shortening of the standard duration and there was also evidence of a reliance on a mixture of absolute and relational strategies in responding.     

Rats’ visual-spatial working memory: New object choice accuracy as a function of number of objects in the study array

When rats had to find new (jackpot) objects for rewards from among previously sampled baited objects, increasing the number of objects in the sample (study) segment of a trial from 3 to 5 and then to 7 (Experiment 1) or from 3 to 6 and 9 (Experiments 2 and 3) or from 6 to 9 and 12 (Experiment 4) did not reduce rats’ test segment performance. Increasing study segment size improved test segment performance contrary the limited-capacity hypothesis concerning rats’ spatial working memory. This effect occurred when objects either differed visually (Experiments 1, 2, 4) or only by odor (Experiment 3). Rats performed no better than chance in finding a jackpot on their first choice from among three visually different objects in Experiments 1 and 2. Furthermore, results from Experiments 2 and 3 indicate that differences in the probability of finding a jackpot by chance in Experiment 1 were not responsible for failure to find the predicted inverse relationship. Results from Experiment 4 indicate that those from Experiments 2 and 3 were not solely due to size of test arrays. We discussed whether our findings could be attributed to innate foraging or perceptual isolation processes during testing or to perceptual encoding processes during exposure to study segment arrays.