rs-79948-197 and Disease-Models--Animal

Disruption of the hypothalamic-pituitary-adrenal axis is an established finding in patients with anxiety and/or depression. Chronic corticosterone administration in animals has been proposed as a model for the study of these stress-related disorders and the antidepressant action. Alterations of the central noradrenergic system and specifically of inhibitory α

Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic Neurons; Animals; Antidepressive Agents, Second-Generation; Brimonidine Tartrate; Cell Body; Corticosterone; Dendrites; Disease Models, Animal; Fluoxetine; Guanosine 5'-O-(3-Thiotriphosphate); Hypothalamo-Hypophyseal System; In Vitro Techniques; Isoquinolines; Locus Coeruleus; Male; Microdialysis; Naphthyridines; Norepinephrine; Pituitary-Adrenal System; Prefrontal Cortex; Presynaptic Terminals; Rats; Receptors, Adrenergic, alpha-2; Stress, Psychological; Sulfur Radioisotopes

Previous findings indicate that post-training administration of the anxiogenic α(2)-adrenoceptor antagonist RS 79948-197 facilitates the consolidation of dorsal striatal-dependent habit memory. The present study examined the effect of concurrent administration of the anxiolytic serotonin 5-HT(1A) receptor partial agonist buspirone on anxiety-induced facilitation of habit memory. Male Long-Evans rats were trained in a response learning version of a water plus-maze task that requires animals to learn to make the same body turn response on each trial in order to reach a hidden escape platform. Immediately following training on days 1-3, rats received peripheral injections of either saline, buspirone (1.5 mg/kg, 2.0 mg/kg, or 5.0 mg/kg), RS 79948-197 (0.1 mg/kg), or RS 79948-197 and buspirone together. Post-training injections of RS 79948-197 alone significantly enhanced memory consolidation. The highest dose of buspirone (5.0 mg/kg) also enhanced response learning. However, concurrent administration of a dose of buspirone (1.5 mg/kg) that itself had no effect on acquisition blocked the memory enhancing effects of RS 79948-197. These findings suggest that the facilitation of habit memory observed following drug-induced anxiety can be prevented by co-administration of an anxiolytic agent.

Topics: Analysis of Variance; Animals; Anti-Anxiety Agents; Anxiety; Buspirone; Disease Models, Animal; Dose-Response Relationship, Drug; Habits; Isoquinolines; Male; Maze Learning; Memory Disorders; Naphthyridines; Rats; Rats, Long-Evans; Time Factors