Aims: The present experiments examined sex differences in ethanol intake and in the influence of a social context on aversive properties of ethanol in adolescent and adult Sprague-Dawley rats. Methods: Experiment 1 examined ethanol intake, with animals receiving daily 2-h access to ethanol and water for 8 days. Experiment 2 assessed the aversive effects of ethanol using a conditioned taste aversion (CTA) paradigm, with animals placed either alone or with a same-sex, same-age peer during the ethanol intoxication phase of conditioning. Results: Ethanol intake varied with both age and sex, although the sex differences emerging at each age were opposite in nature. Adolescent males consumed more ethanol relative to their body weights than adolescent females and adults of both sexes, whereas adult females generally consumed more than adult males. The CTA test revealed no sex differences in aversive effects of ethanol in adults, whereas adolescent males were less sensitive to the aversive properties of ethanol than adolescent females when intoxication occurred in the presence of a peer. Ethanol-induced CTA was evident in adults at lower doses than in adolescents. Conclusions: These results suggest that age differences in ethanol intake in males and sex differences in intake during adolescence may be associated in part with the relative insensitivity of the male adolescents to ethanol's aversive properties, especially when intoxication occurred in a social context. However, the elevated ethanol intake observed in adult females relative to their male counterparts appears to be unrelated to the aversive properties of ethanol.

The extent to which characteristic adolescent behaviors are associated with pubertal changes or driven by more general, puberty-independent developmental alterations is largely unknown. Using physiological and hormonal markers of puberty, this experiment characterized pubertal timing across adolescence and examined the relationships among these variables and novelty-directed behaviors. Males and females were tested for response to novelty at P28, P32, P36, P40, P44, P48 and P75, and examined for balano-preputial skinfold separation and sperm presence (males) or vaginal opening (females), followed by blood collection for hormonal assessments. Despite earlier pubertal maturation in females, with maturation generally completed by P36 in females and P44 in males, novelty-directed behavior peaked at P32 and P36 in both sexes, and was unrelated to pubertal measures. These data support the suggestion that the ontogenetic peak in this behavior during adolescence is not notably puberty-dependent.

Background Ethanol intake levels characteristic of adult males and females emerge post-pubertally. The present set of experiments examined the consequences of pre-pubertal and adult gonadectomies to explore whether the presence of gonadal hormones at puberty exerts organizational influences and/or plays an activational role in age- and sex-typical patterns of ethanol consumption. Methods Male and female Sprague-Dawley rats were gonadectomized (GX), received sham gonadectomy (SH) or were left non-manipulated (NM) at one of two ages, either pre-pubertally on postnatal day (P) 23 (early) or post-pubertally in adulthood on P70 (late). Early surgery animals were tested for ethanol consumption either during adolescence (P28-39) or in adulthood at the same age that late surgery animals were tested (P75-86). Voluntary ethanol consumption was indexed using a 2 hr limited-access paradigm, with access to two bottles: one containing water, and the other a sweetened ethanol solution. Results Age of GX did not impact patterns of ethanol consumption. Removal of testicular hormones in males, regardless of age of removal, elevated consumption levels in adulthood to female-typical levels. Ovariectomy did not have notable effects on ethanol drinking in females. Ethanol intake and preference of early SH males was significantly greater than that of both late SH and NM males. Removal of the gonads prior to puberty did not influence ethanol drinking or preference during adolescence in either males or females. Conclusions These results suggest that testicular hormones play an activational role in lowering ethanol intake and preference of adult male rats. Pubertal hormones, in contrast, were found to exert little influence on ethanol drinking or preference during adolescence, although the effect of surgical manipulation itself during development was found to exert a long-lasting facilitatory effect on ethanol consumption in adulthood.

Sex- and age-typical responses to ethanol and novel stimuli tend to emerge postpubertally, suggesting a potential organizational or activational role for pubertal hormones in these behaviors. To test this possibility, male and female rats were gonadectomized (GX) or received sham gonadectomy (SH) either prepubertally on postnatal day (P) 23 (early) or in adulthood on P70 (late). Animals were tested as adults for response to novelty and, on the following day, challenged with either saline or ethanol (1g/kg) prior to social interaction testing with an unfamiliar partner in a familiar setting under low light conditions. Gonadectomy did not influence ethanol-induced social inhibition in either sex, but instead altered the microstructure of social behavior, with GX animals exhibiting proportionally less time in social investigation and proportionally more time in contact behavior than SH animals, regardless of age of gonadectomy. The early sham surgical manipulation process itself influenced social motivation, with early SH surgery eliminating ethanol-induced decreases in social preference in both sexes. Response to novelty was unaffected by gonadectomy, but was suppressed in early compared to late SH manipulated animals. These results suggest that adult-typical responses to ethanol and novelty-directed behaviors are little influenced by gonadal hormones during puberty or in adulthood. However, the experience of surgical manipulation itself during development exerts behavioral and pharmacological consequences that last into adulthood.

Previous studies have shown that adult female rats consume more ethanol than adult males. Castration of male rats has been found to increase their ethanol intake and preference to levels significantly elevated above their sham-gonadectomized counterparts and similar to levels observed in females. The purpose of the present experiment was to examine whether testosterone replacement in castrated adult male rats would be sufficient to restore the relatively low levels of ethanol drinking characteristic of intact adult male rats. Males were either gonadectomized and implanted with a testosterone propionate pellet (RPL), gonadectomized and implanted with a placebo pellet (GX), sham-gonadectomized and implanted with a placebo pellet (SH), or were left non-manipulated (NM). Voluntary ethanol intake was measured using a 2 hr limited-access drinking paradigm, with access to two bottles: one containing water, and the other a sweetened ethanol solution. Hormone replacement was sufficient to return ethanol intake and preference of castrates to levels comparable to both SH and NM control males. Ethanol preference of RPL males was also significantly suppressed compared to GX males by the end of the measurement period, whereas these group comparisons did not reach statistical significance for g/kg ethanol intake. These data suggest that testosterone serves to suppress ethanol preference in male rats, and may contribute to the sex differences in ethanol preference and consumption commonly reported in adult rats.