5-HT(1A) receptor subsensitivity in infancy and supersensitivity in adulthood in an animal model of depression.

Flinders Sensitive Line (FSL) rats, a genetic animal model of depression, exhibit 5-HT abnormalities including an increased sensitivity to serotonergic agonists. Studies of 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT)-induced hypothermia have shown 5-HT(1A) receptor supersensitivity in adult FSL rats. The aims of the present study were to: (a) further characterize the 5-HT(1A) system in adult FSL rats by assessing their behavioral responses to 8-OH-DPAT (the 'serotonergic syndrome'-a pattern of stereotypic behavior on a number of parameters). (b) Examine behavioral and hypothermic responses of neonatal FSL pups to 8-OH-DPAT. In adult FSL rats the 'serotonergic syndrome' was measured (Exp. 1) and in 1-day-old pups body temperature and ultrasonic vocalizations (USV) were also examined (Exp. 2) following administration (s.c. and i.p., respectively) of 8-OH-DPAT (1 mg/kg). Overall, adult FSL rats exhibited a significant supersensitive behavioral response to 8-OH-DPAT compared to Sprague-Dawley controls. Under baseline conditions, body weight, USV and rectal temperature were significantly lower in FSL pups compared to controls. In contrast to the adults, 1-day-old FSL pups exhibited an overall pattern of subsensitive stereotypic response to the agonist. In conclusion, an abnormal pattern of response to 8-OH-DPAT was observable in FSL rats, as early as postnatal day 1. This may contribute to a better understanding of the involvement of the serotonergic system in depression, and lead to pharmacological interventions aiming to modulate 5-HT regulation.