EFFECTS OF PIVAGABINE ON PSYCHOPHYSICAL PERFORMANCE AND BEHAVIORAL-RESPONSE IN EXPERIMENTAL-MODELS OF STRESS

The effect of pivagabine (4-[(2.2-dimethyl-1-oxopropyl)amino]butanoic acid. CAS 69542-93-4, Tonerg(R)), a synthetic molecule with neuromodul atory activity, was evaluated on a series of behavioural parameters in rats exposed to various stimuli, with the aim of evaluating the respo nse to stress (open field exploration, water maze, psychic conflict). conditioning (active and passive avoidance and avoidance retention, ag gressiveness, extinction of conditioned responses), learning and perfo rming of specific psychophysical tests (rota-rod, ballasted swimming, taut thread). Pivagabine induced significant improvement of stress-rel ated tests by reducing the anxiety-producing reactions related to the various experimental settings. In conditioning tests an improvement in learning of conditioned responses was observed at lower dosages (10 a nd 50 mg/kg); an opposite effect was obtained with higher dosages (100 and 200 mg/kg), Pivagabine did not influence the retention nor the ex tinction of conditioned responses, Pivagabine induced a marked improve ment of all motor performance tests in young and in aged animals, ac-c ontrast with benzodiazepines, pivagabine did not alter the ability of learning tasks, the motor performance and the aggressive behaviours. I t is likely that the observed effects of pivagabine are mediated by in hibition of release of corticotropin-releasing factor, a neurohormone involved in stress-generating mechanisms.