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Prenatal ethanol exposure in rats alters serotonergic-mediated behavioral and physiological function


Rationale. 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-HT1A and 5-HT2A receptor function, two 5-HT receptor subtypes mediating these behaviors. We measured the physiological and behavioral responses to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the 5-HT2A/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-HT1A and 5-HT2A 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.

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Hofmann, C., Simms, W., Yu, W. et al. Prenatal ethanol exposure in rats alters serotonergic-mediated behavioral and physiological function. Psychopharmacology 161, 379–386 (2002).

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  • Prenatal ethanol exposure Serotonin receptor Wet-dog shakes Hypothermia