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.
Shayit
Michal
M
Department of Psychology, Bar Ilan University, Ramat-Gan, Israel.
Yadid
Gal
G
Overstreet
David H
DH
Weller
Aron
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism*; D004195:Disease Models, Animal; D007035:Hypothermia / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014828:Vocalization, Animal / Q000187:drug effects
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin