Effects of RGH 2202 on cognitive and motor behavior of the rat

Abstract The behavioral activity of the thyrotropin-releasing hormone (TRH) analogue, L-6-ketopiperidine-2-carbonyl-leucyl-L-prolinamide (RGH 2202), has been studied in animal models of central neurotransmission disruption. In 24-month-old rats, repeated administration of the peptide (5 or 10 mg/kg/day, injected IP for 20 days) was followed by a facilitated acquisition of active avoidance behavior in the shuttle-box test and retention of passive avoidance reaction in a step-through passive avoidance task. Also, ambulation in an open field was increased and motor performance and co-ordination in the rotorod test was facilitated by the treatment. Scopolamine-induced amnesia was reverted by RGH 2202 in adult rats tested both in active and passive avoidance tasks. Cognitive deficits induced in rats by prenatal manipulation with methylazoxymethanol (MAM) were reduced in adulthood by repeated administration with RGH 2202. These results indicate that the TRH-analogue, RGH 2202 may improve cognitive and motor disturbances in aging or induced by central neurotransmission disruption. It is possible that the peptide is functioning, at least in part, by intervening with the central cholinergic neurotransmission.