Behavioral and neural biology最新文献

We previously reported that systemically administered N-methyl-d-aspartate (NMDA) antagonists significantly impair spontaneous alternation behavior. Others have reported that the restricted blockade of hippocampal NMDA receptors disrupts performance on different tests of spatial learning and have suggested that the resulting impairments are attributable to a disruption of endogenous NMDA-dependent long-term potentiation (LTP). In the present study, we determined whether spontaneous alternation performance was disrupted by circumscribed blockade of hippocampal NMDA receptors as well as by a second class of compounds which disrupt LTP, protein kinase inhibitors. The effect of hippocampal NMDA blockade on inhibitory avoidance was also examined insofar as this behavior too is disrupted by systemically administered NMDA antagonists. When injected into the hippocampus 15 min prior to spontaneous alternation testing, the NMDA antagonists CPP and d,l-AP5 each decreased alternation rates. the specific protein kinase C (PKC) inhibitor, NPC 15437, also disrupted spontaneous alternation, whereas the more general kinase inhibitor, PMXB, did not. When injected 15 min prior to inhibitory avoidance training, CPP also impaired inhibitory avoidance learning as assessed during a subsequent test session, 48 h later. Interpretation of these data was complicated by the additional findings that intrahippocampal infusion of l-AP5 (which is inactive with respect to NMDA receptors) also disrupted alternation performance, and that both the d- and the l-isomers of AP5 as well as each kinase inhibitor dramatically disrupted evoked responses (i.e., population spike amplitude, spike latency, and EPSP slope), as recorded in the dentate gyrus and evoked by perforant path stimulation. These data indicate that behaviorally effective doses of AP5 may have effects which extend beyond NMDA blockade. Moreover, the effects of these compounds on hippocampal transmission, in general, suggest that attribution of the amnestic consequences of their administration to impaired LTP may be unwarranted.

Deficits in associative functions seen with senescence may be based, at least in part, on a decreased availability of trophic factors in the CNS. A reduced concentration of neurokinins, including undecapeptide substance P (SP), also accompanies aging. Thus, given the change in SP metabolism and the known mnemogenic as well as neurotrophic/neuroprotective effects of the peptide, it seems possible that age-related deficits in associative processes could be influenced by treatment with exogenous SP. In the present study, 30-month-old Wistar rats were injected daily with SP (50 or 250 μg/kg, intraperitoneally) starting 1 week before they were tested on the Morris water maze task and on motor coordination tests. Control groups included vehicle-injected old and adult (3-month-old) rats. Over the days of maze testing, application of the substances was performed 5 h after testing daily for 15 days and after the last drug delivery, maze testing was continued for 4 more days. The main finding of this study is that chronic administration of both dosages of SP (50 and 250 μg/kg) improved the maze performance of the old rats. This facilitatory effect of SP on performance was also evident after the drug treatment had been terminated in the course of maze testing. Furthermore, chronic application of SP in a dose range of 50–250 μg/kg was found to reduce age-related deficits in motor capacities.

Prior research has shown that a conditioned antinociceptive response can be established in spinalized rats by pairing stimulation to one hind leg (the conditioned stimulus, or CS) with tailshock (the unconditioned stimulus, or US). This suggests that spinal mechanisms can support classical conditioning. It is well known that in intact subjects, classical conditioning is undermined by preexposure to the CS (latent inhibition) or the concurrent presentation of either a more salient CS (overshadowing) or one that has already been associated with the US (blocking). In the present paper we show that these manipulations have a similar impact on the acquisition of a conditioned antinociceptive response in spinalized rats. These findings imply that similar principles may govern the acquisition of a conditioned response across different levels of the nervous system.

Potent and highly selective adenosine A₁ and A₂ receptor agonists were bilaterally injected into the nucleus accumbens of mice 10 min prior to inhibitory avoidance training. Retention of the inhibitory avoidance response was assessed 24 h after training. Intra-ACB activation of A₁ receptors, but not A_2a receptor activation, significantly impaired the performance of mice during the subsequent retention test. Furthermore, the retention deficit produced by activation of A₁ receptors was significantly attenuated by pretreating mice with a highly selective A₁ receptor antagonist. These findings suggest that endogenous adenosine may modulate information processing in the ventral striatum via adenosine A₁ receptors.

Platelet-activating factor (PAF) is present in the brain.It enhances glutamate release and long-term potentiation (LTP) through an action on synaptic membrane receptors sensitive to the antagonist, BN 52021, and has been proposed as a retrograde messenger in the genesis of LTP. In addition, PAF has other, metabolic actions mediated by microsomal receptors sensitive to the antagonist, BN 50730. We investigated the effect on memory of the preor post-training infusion of BN 52021 or BN 50730 into the hippocampus and that of BN 52021 in the amygdala and the entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae aimed at these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.5-mA foot shock and tested for retention 24 h later. BN 52021 (0.5 μg/side) was amnestic when given into the hippocampus or the amygdala either before or immediately after training but not 30 or 100 min later. BN 52021 was also amnestic when given into the entorhinal cortex 100 but not 0 or 300 min after training. Intrahippocampally administered BN 50730 had no effect on memory. The findings are compatible with the suggestion from previous findings that memory of this task depends on the generation of LTP at the time of training in hippocampus and amygdala and, 90–180 min later, in the entorhinal cortex.

Previous studies indicate that somatosensory inputs to the snout and the ventral trunk play critical roles in the elicitation and maintenance of maternal aggression by postpartum lactating Long-Evans Norway rats toward a strange male intruder. In the present studies we examined the possible influence of visual and auditory stimuli in the display of this behavior. In Experiment 1, dams temporarily deprived of visual or auditory input by eyelid suturing or ear molds, respectively, on Day 2 postpartum, were found to have normal levels of maternal aggression 1 day later. In Experiment 2, males were found to contribute about 50% of the short-duration 50-kHz vocalizations, which begin shortly after introduction of the intruder, and all of the long-duration 22-kHz vocalizations, which begin after the onset of attacks. Nonetheless, females tested with males surgically devocalized 7 days earlier were not significantly different in aggressiveness from dams tested with vocalizing males on either Day 1 or Day 4 postpartum. These findings indicate that visual or auditory inputs from the pups or intruder are not critical to the display of maternal aggression in rats, at least within the confines of laboratory housing.

It was recently reported that administration of relatively high intensities of footshock (overreinforcement) during training of passive avoidance protected animals against the amnesic effect of scopolamine, injected 5 min after training. This was interpreted in terms of a lesser involvement of acetylcholine in memory consolidation. An alternative explanation was that overreinforcement accelerated the consolidation process, which could have taken place before the injection of scopolamine. To test for this possibility, male Wistar rats were injected with 4, 8, or 12 mg/kg of scopolamine, 5 min before training with low or high levels of footshock and then tested for retention of the task. Scopolamine induced the expected memory deficit after the low-intensity footshock; after overreinforcement the higher doses of scopolamine induced state dependency, while no deficits were produced with the lower dose. It was concluded that: (a) acetylcholine is indeed involved in memory consolidation of passive avoidance; (b) scopolamine interacts with high footshock levels to produce state dependency; and (c) when relatively low doses of scopolamine are used in conditions of overreinforcement, protection against scopolamine-induced amnesia becomes evident.

Previous work from our laboratory indicated that emergence neophobia is highly correlated with perforant path long-term potentiation (LTP) in rats. In the present study, we examined the relationship between hippocampal and cortical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors and emergence behavior in rats. Emergence neophobia was assessed in an exploratory task that provided a choice between a novel alley and a familiar nest box. Quantitative autoradiography using radiolabeled ligands specific for the AMPA subclass of glutamate receptors was performed on frozen brain sections. Both [³H]AMPA and [³H]CNQX (6-cyano-7-nitro-[³H]quinoxaline-2,3-dione, an AMPA receptor antagonist) binding in the dentate gyrus (stratum moleculare), hippocampal area CA1 (stratum radiatum), and the parietal cortex overlying the hippocampus were significantly correlated with emergence behavior. The correlations indicated that neophobic rats, which had longer latencies to enter the novel alley, made fewer entries into the alley, and spent less time in the novel alley during a 10-min test than their neophilic counterparts, had higher levels of AMPA receptor binding. These results suggest that individual differences in specific hippocampal AMPA receptors reflect variability in a specific class of hippocampal-dependent behaviors.

The present experiment sought to evaluate the contribution of the ventrolateral periaqueductal gray to the expression of the conditioned bradycardic heart rate response in the rabbit. This response occurs in the presence of a fear-arousing conditioned stimulus. Lesions of the ventrolateral periaqueductal gray made after training failed to affect retention of the conditioned response. The results suggest that this region of the midbrain plays a nonessential role in the expression of the conditioned bradycardic response.

Micrencephalic Sprague-Dawley rats were produced byan injection of 20 mg/kg methylazoxymethanol acetate on gestational Day 14. Brain weights of the offspring were 70% of controls while weights of frontal cortex and hippocampus were approximately 58% (Ferguson, Racey, Paule, & Holson, 1993). Operant perforamnce was measured with particular emphasis on assessment of time estimation. The temporal response differentiation (TRD) and the progressive ratio (PR) tasks, previously used in the NCTR operant test battery for monkeys, were chosen for evaluation. The TRD schedule is notably different from other temporal tasks in that it requires subjects to initiate and maintain a lever press for 10–14 s. The PR task was included as a measure of motivation to work for food reinforcers. Micrencephalics acquired and performed both tasks comparably to controls. During extinction, however, micrencephalics exhibited an increased TRD lever hold duration. This suggests an atypical response perseveration, that is, perserverating the previously correct response. Previously, frontal cortical alterations were suggested to contribute heavily to micrencephalic-induced behavioral alterations (Ferguson et al., 1993). This study provides further evidence that response perseveration, a hallmark of frontal cortical lesions, is expressed in micrencephalic rats.