Assessment of neuroleptic-like properties of progesterone

There is considerable evidence from epidemiological studies that the onset of psychiatric disorders may be related to changes in the secretion of gona dal hormones. For example, the postpartum period appears to be a vulnerable phase for the occurrence of psychiatric disturbances such as dysphoric moo d and even severe psychotic disturbances. It has been suggested that a sudd en drop in progesterone concentrations may contribute to the development of such disorders. Because the administration of this steroid might be of the rapeutic value in psychiatric disturbances, we investigated the behavioral properties of progesterone in the rat to assess putative neuroleptic-like p roperties of this steroid. Progesterone administration dose-dependently inc reased the EEG activity during wakefulness in the 10- to 30-Hz frequency ba nds and decreased locomotor activity. While no anxiolytic activity could be detected in the plus maze, the highest dose of progesterone (90 mg/kg) exe rted an inhibitory effect on the conditioned avoidance response. In contras t to haloperidol (0.5 mg/kg), progesterone neither produced catalepsy nor a ntagonized amphetamine-induced stereotypy. However, both progesterone (10, 30 and 90 mg/kg) and haloperidol (0.1 mg/kg) effectively restored the disru ption of the prepulse inhibition (PPI) of the acoustic startle response (AS R) that was evoked by apomorphine (2 mg/kg). In contrast, allopregnanolone (10 mg/kg), one of the main metabolites of progesterone, did not significan tly antagonize the effect of apomorphine on the PPI. This behavioral profil e of progesterone is compatible with the sedative properties of its metabol ite allopregnanolone via the GABA(A) receptor but also with the possibility that progesterone itself shares some properties with atypical antipsychoti cs, which may be relevant for the development and treatment of psychotic di sturbances.