Prenatal ethanol exposure in rats alters serotonergic-mediated behavioral and physiological function.
BACKGROUND
Animals prenatally exposed to ethanol (ethanol-exposed animals) exhibit physiological and behavioral abnormalities consistent with altered 5-hyrdroxytryptamine (5-HT) function including lack of response inhibition and increased anxiety and aggression.


OBJECTIVE
The present study investigated the possibility that ethanol-exposed animals show alterations in 5-HT(1A) and 5-HT(2A) receptor function, two 5-HT receptor subtypes mediating these behaviors. We measured the physiological and behavioral responses to the 5-HT(1A) agonist 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), and the 5-HT(2A/C)agonist (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride) (DOI), which provide indices for estimating central changes in 5-HT activity and receptor function.


METHODS
Female and male offspring from ethanol-exposed (E), pair-fed control (PF), and ad-libitum-fed control (C) dams were tested in adulthood. Animals were injected with 8-OH-DPAT or DOI to induce hypothermia and wet-dog shakes (WDS, a paroxysmal shudder of the head, neck and trunk), respectively, or with saline. In experiment 1, core temperatures were recorded immediately before injection of 8-OH-DPAT (0, 0.125 mg/kg or 0.500 mg/kg) and again at 30, 60, 90, 120 and 180 min post-injection. In experiment 2, the number of WDS were recorded in response to injection of DOI (0, 1 mg/kg).


RESULTS
E females and males showed a greater hypothermic response to 8-OH-DPAT than PF and C animals. E females and males also showed less of a differential hypothermic response to low and high doses of 8-OH-DPAT than PF and C animals. In addition, in response to DOI, E females, but not males, showed a significantly greater rate of WDS than PF and C females.


CONCLUSIONS
Our findings indicate that prenatal ethanol exposure alters 5-HT(1A) and 5-HT(2A) receptor function in adulthood and does so in a sex-specific manner. These findings have important implications for altered hormonal and behavioral responsiveness observed in ethanol-exposed animals.
Hofmann
Candace E
CE
Department of Anatomy, University of British Columbia, 2177 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z1.
Simms
Wendy
W
Yu
Wayne K
WK
Weinberg
Joanne
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012737:Sex Factors
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol