CRF IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS INDUCES DOSE-RELATED BEHAVIORAL PROFILE IN RATS

Corticotropin-releasing factor (CRF) administered into the cerebrospinal fluid (CSF) alters grooming and locomotion in rats. The present study was designed to investigate if CRF microinjected into the paraventricular nucleus of the hypothalamus (PVN) influences grooming and spontaneous locomotor behavior in fasted rats maintained in a familiar environment. Unilateral microinfusion of CRF (0.06, 0.2 and 0.6 nmol) into the PVN induced a dose-related increase in grooming, whereas locomotion was dually affected. At lower doses of CRF (0.06 and 0.2 nmol) spontaneous locomotion was significantly increased. At the highest dose, locomotor activity was markedly reduced and, in about 30% of animals, freezing behavior occurred intermittently. The behavioral effects of CRF were maintained throughout the 60 min post injection period. Microinjection of CRF (0.2 nmol) into the lateral hypothalamus, or outside of PVN boundaries had no effect on these behavioral parameters. These results demonstrate that the PVN is a selective and potent site of action for CRF to induce a dose-dependent range of alterations in grooming and locomotion that mimics those observed after CSF injection in a familiar environment. These data also suggest that CRF in the PVN may be involved in mediating behavioral activation and the anxiogenic effect.