EFFECTS OF RGH-2202 ON COGNITIVE AND MOTOR BEHAVIOR OF THE RAT

The behavioral activity of the thyrorropin-releasing hormone (TRH) ana logue, L-6-ketopiperidine-2-carbonyl-leucyl-L-prolinamide (RGH 2202), has been studied in animal models of central neurotransmission disrupt ion. In 24-month-old rats, repeated administration of the peptide (5 o r 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 avoi dance task. Also, ambulation in an open field was increased and motor performance and co-ordination in the rotorod test was facilitated by t he treatment. Scopolamine-induced amnesia was reverted by RGH 2202 in adult rats tested both in active and passive avoidance tasks. Cognitiv e deficits induced in rats by prenatal manipulation with methylazoxyme thanol (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 centra l neurotransmission disruption. It is possible that the peptide is fun ctioning, at least in part, by intervening with the central cholinergi c neurotransmission.