Emine Babar

Effects of ketamine on different types of anxiety/fear and related memory in rats with lesions of the median raphe nucleus

The aim of the present study was to determine the involvement of the median raphe serotonergic system in the effects of ketamine on anxiety behaviours and related memory. The effects of ketamine pretreatment (3 and 10 mg/kg, i.p.) on three types of fear-motivated behaviours, unconditioned one-way escape, conditioned avoidance and freezing were tested. Experiments were performed with the inhibitory avoidance apparatus in rats with ibotenic acid lesions of the median raphe nucleus. It was found that 10 mg/kg ketamine had an anxiogenic-like effect on one-way escape type of fear and anxiolytic-like effect on conditioned freezing-related fear; these effects were unaffected by median raphe lesions. Both ketamine doses impaired freezing-related fear memory. Ketamine (10 mg/kg) also produced an anxiolytic-like effect on avoidance type of fear and impaired avoidance memory. The median raphe lesions attenuated the anxiolytic action of the drug on the avoidance type of fear and prevented ketamine-induced avoidance memory impairment. These results suggest that the anxiolytic-like effect of ketamine on avoidance-type fear is mediated through the median raphe serotonergic system.

Hypofunction of the dorsal hippocampal NMDA receptors impairs retrieval of memory to partially presented foreground context in a single-trial fear conditioning in rats

In the present study, the effects of N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonopentanoic acid (AP5) bilaterally infused into the dorsal hippocampus (2.0 microl /5 microg), on the retrieval of fear memory to partial and whole foreground cues were evaluated by using a step-through passive avoidance and Pavlovian fear conditioning. In the both conditioning tasks, following a 30-s preshock exposure period to the shock-associated context, rats received a single shock in a foreground manner for fear memory exhibition by freezing. Rats with AP5 infusion 5 min before the retrieval tests showed profound freezing deficits either immediately or 48 h after the shock in the testing section of the passive avoidance chamber where foreground cues was partially presented. In the Pavlovian conditioning chamber where fear conditioning was tested in the whole of the context that was explicitly paired with the shock, AP5 rats in all infusion schedules exhibited robust freezing responses. These results showed that hypofunction of the hippocampal NMDA receptors impaired the retrieval of fear memory to partial, and not whole, foreground cues. This suggests that NMDA receptors of the hippocampus are involved in the formation of background context representations about foreground events when there is a deficit in perceiving certain sensory properties of the foreground retrieval cues.

Effects of excitotoxic median raphe lesion on working memory deficits produced by the dorsal hippocampal muscarinic receptor blockade in the inhibitory avoidance in rats.

The experiments investigated the interactions between median raphe nucleus (MRN) serotonergic and septo-hippocampal muscarinic cholinergic systems in the modulation of forming and storing performances of working memory. Rats with ibotenic acid-induced MRN-lesion bilaterally received scopolamine (2-4 microg/each side) infusion into the dentate gyrus of the dorsal hippocampus and were tested in a single trial step-through inhibitory avoidance. Initial preference to the dark compartment (escape latency) was taken as the measure of non-mnemonic behaviours and response latency to enter the dark compartment immediately after the foot-shock was used to measure working memory. The high-dose scopolamine infusion 10 min before the training decreased escape latencies in the sham-lesioned rats, whereas had no effect in the MRN-lesioned rats. Although MRN lesion per se did not alter response latency, it alleviated pre-training scopolamine-induced decrease, but aggravated post-training scopolamine-induced reduction in this parameter. These results suggest that the antagonistic interactive processes between MRN-serotonergic and hippocampal cholinergic systems modulate non-mnemonic component of working memory formation, whereas the storing performance of working memory is modulated by the synergistic interactions between these systems in the hippocampus, mainly in the dentate gyrus.

Enriched environment has limited capacity for the correction of hippocampal memory-dependent schizoid behaviors in rats with early postnatal NMDAR dysfunction.

Pre‐ and early postnatal stress can cause dysfunction of the N‐methyl‐d‐aspartate receptor (NMDAR) and thereby promote the development of hippocampus memory‐dependent schizoid abnormalities of navigation in space, time, and knowledge. An enriched environment improves mental abilities in humans and animals. Whether an enriched environment can prevent the development of schizoid symptoms induced by neonatal NMDAR dysfunction was the central question of our paper. The experimental animals were Wistar rats. Early postnatal NMDAR dysfunction was created by systemic treatment of rat pups with the NMDAR antagonist MK‐801 at PD10–20 days. During the development period (PD21–90 days), the rats were reared in cognitively and physically enriched cages. Adult age rats were tested on navigation based on pattern separation and episodic memory in the open field and on auto‐hetero‐associations based on episodic and semantic memory in a step‐through passive avoidance task. The results showed that postnatal NMDAR antagonism caused abnormal behaviors in both tests. An enriched environment prevented deficits in the development of navigation in space based on pattern separation and hetero‐associations based on semantic memory. However, an enriched environment was unable to rescue navigation in space and auto‐associations based on episodic memory. These data may contribute to the understanding that an enriched environment has a limited capacity for therapeutic interventions in protecting the development of schizoid syndromes in children and adolescents.

EFFECTS OF EXCITOTOXIC MEDIAN RAPHE LESIONS ON SCOPOLAMINE-INDUCED WORKING MEMORY DEFICITS IN INHIBITORY AVOIDANCE

The aim of the present study was to investigate the effects of excitotoxic damage of the serotonergic cell bodies in the median raphe nucleus (MRN) on the scopolamine-induced working memory deficits in a single-trial light/dark inhibitory avoidance task. Rats were given 1 mg/kg of scopolamine hydrobromide (intraperitonal, IP) or saline before the inhibitory avoidance training, in which initial preference to the dark compartment (escape latency) was used to measure nonmnemonic behaviors, and response latency to enter the dark compartment immediately after the shock was used to measure working memory. It was found that scopolamine significantly reduced escape latencies in sham-lesioned rats, whereas it had no effect in the rats with MRN lesions. Although MRN lesion per se did not alter response latency, it prevented scopolamine-induced decrease in this parameter. These results suggest that the antagonistic interactive processes between serotonergic projections of the MRN and the muscarinic cholinergic system modulate nonmnemonic attentional component of working memory formation in the inhibitory avoidance.

A comparative study on the influence of estrous cycle on cognitive and coping behaviors in rats

Materials and methods The present study was investigate the influence of estrous cycle in adult female Wistar rats on the responses to emergency novelty by using an open field (OF) and on the recognition of fearful partial or whole cues presented during testing in the passive avoidance (PA) apparatus. In conditioning task, rats recieved a single shock (1 mA) following a 30-s preshock exposure period to the shock associated context of the PA. Estrous cycle phases were determined by vaginal lavage.

Effects of NMDA receptor blockade in early developmental period on emotional behaviors in adult social isolated rats reared in physical barren and enriched conditions

increase in time spent in the close arms (P<0.05) with increases in ethological type of exploratory behaviors (head streached, P<0.05; upward exploratory behavior, P<0.001; and self-grooming P<0.05), compared to the SI rats reared barren environment. NMDA receptor blockade attenuates the effects of physical enrichment in the EPM. Conclusions These findings indicate that NMDA receptor blockade in the last maturation period of brain development is implicated in forming multiple associations with environment.

A new method for studying developmental factors in cognitive and emotional behaviors in adult mice

Background It is recognized that mental-emotional diseases can be caused by disturbances of cognitive processes of matching between the current and stored spatial information [1]. Cognitive matching processor is activited in rodents also during a stereotype upward behavior (rears) [2]. In the present study, we used a new method for studing the effects behavioral dissection of rears in developmental period (BDRD) on cognitive and emotional responses of adult mice.