Effects of fluoxetine on memory processes in rats with different phenotypes of the nervous system and different levels of biogenic monoamines of the brain
Mohammad Reza Majidi
Background: Seizures formed in response to a sound in rats allows studying the mechanisms of both occurrence of pathological seizure activity and anti-seizure effects of new medications. Contemporary antidepressants are targeted at enhancing the level of the main neurotransmitters in the brain. One of the important biochemical factors forming mixed anxiety-depressive disorders is serotonin (5-HT). Deficiency of 5-HT leads to impairment of synaptic transmission in neurons of the CNS and forms depressive states. Among the drugs that affect 5-HT synaptic transmission, the leading role is given to selective serotonin reuptake inhibitors, such as fluoxetine. The present paper explores the effects of the psychopharmacological agent - fluoxetine - on mnestic processes, using a model of passive avoidance on male Wistar rats with different nervous system phenotypes and different activity ratios of the monoaminergic systems of the brains. Methods: The Wistar rats (body mass of 180-220 g) were preliminarily tested for tolerance to acoustic startle stimulus. The difference in the responses to acoustic stimulus allowed dividing the animals into 2 groups: seizure-sensitive (SS – prone to seizures) and seizure-tolerant (ST – without motor excitati-on) ratsSS rats were selected. Both types of the ani-mals were divided into the experimental and cont-rol animals. 1 h prior to the experiment, the experimental animals were intra peritoneally injected with fluoxetine (Pharma science, Montreal, Canada) at a dose of 25mg/kg. The control Rats weread ministered with the diluent distilled water in the equal volume. Results: control ST rats compared to the SS ones had lower rate of PA response retention. However, under administration of fluoxetine, the lower rate of response retention was observed in the SS rats compared to the ST ones. The number of entries to the dark compartment was larger in the SS rats compared to the ST ones. Thus, one part of the SS rats entered and left the dark compartment for several times, while the other part entered immediately the dark compartment and stayed there until the end of the experiment, demonstrating an impairment of retention of the formed response. In the retest session under administration of fluoxetine, the seizure- tolerant rats compared to the seizure-sensitive rats were characterized by a more pronounced fear response to the "unsafe" compartment and enhanced anxiety facilitating the retention of memory trace. Acute administration of fluoxetine led to the opposite effects on memory traces retrieval in the experimental animals of both types. Conclusion: The individual sensitivity of the animals to the action of the psychopharmacological agent fluoxetine and the direction of its effects on mnestic processes are supposed to be associated by different primary activity ratios of the MA-ergic systems of the brain.