Pre-pubertal gonadectomy and the social consequences of acute ethanol in adolescent male and female rats

Abstract

It has previously been shown that pre-pubertal or adult gonadectomy (GX) increases ethanol intake in male rats. This study examined whether this sex-selective increase reflects a GX-induced maintenance in males of more adolescent-typical responsiveness to ethanol characterized by enhanced sensitivity to positive (e.g., socially facilitating) and a decreased sensitivity to adverse (e.g., socially inhibitory) effects of ethanol. Male and female Sprague-Dawley rats were prepubertally GX, sham (SH)-operated, or non-manipulated (NM) at postnatal day (P) 25. During the late adolescent transition into adulthood (P48 -- baseline day), rats were given a saline injection, placed alone into a familiar test apparatus for 30 min and then exposed for 10 min to an unfamiliar partner of the same age and sex. On the following day (P49), similar testing occurred after administration of 0.5, 0.75, 1.0 or 1.25 g/kg ethanol. At baseline, GX males and females displayed higher levels of social activity (especially adolescent-typical play and contact behavior) than SH and NM animals, with GX females displaying greater social activity than GX males. Neither males nor females demonstrated social facilitation at lower ethanol doses, regardless of hormonal status. Whereas the social inhibitory effects of higher doses of ethanol were similar across groups among females, SH males were less sensitive than both GX and NM males to ethanol-induced social inhibition. These results suggest that enhanced ethanol intake in GX males is not related to alterations in sensitivity to ethanol’s social inhibitory effects. GX, however, results in retention of adolescent-typical social behaviors, with older GX adolescent rats resembling early adolescents in exhibiting elevated social activity—particularly play and contact behavior.

Sex-dependent consequences of pre-pubertal gonadectomy: Social behavior, stress and ethanol responsivity

“…A recent study by Torres et al, (2014) reported that GX in females eliminated ethanol conditioned place preference, suggesting a potential role for estradiol in mediating the rewarding properties of ethanol, although the effects of GX on ethanol intake was not explored. In contrast, in our work to date, we have been unable to detect notable effects of GX on various alcohol sensitivities thought to influence intake and hence potentially contribute to sex-dependent differences in ethanol intake (Morales et al, 2014b; Vetter-O’ Hagen and Spear, 2012), although the effects of stressors and social context on GX/ethanol interactions have yet to be explored. The purpose of this study, therefore, was to investigate sex differences in the role of pre-pubertal GX on interactions between ethanol and social stimuli via examining sensitivity to: a) the social impairing effects of ethanol following acute restraint stress; as well as b) the aversive effects of ethanol when conditioning/testing occurs within a social context.…”

“…Previous studies have not found significant differences in BECs (Vetter-O’ Hagen and Spear, 2012) or brain ethanol concentrations (Morales et al, 2014b) between GX and control females. However, drug bioavailability and distribution can be influenced by the presence of estrogen.…”

“…Given that males and females differ notably in their responses to stressors (Kirschbaum et al, 1992; Kudielka and Kirschbaum, 2005; Shors et al, 2001; Solomon and Herman, 2009) and the impact of a social setting on ethanol sensitivity (Douglas et al, 2004; Morales et al, 2014b; Varlinskaya et al, 2015), the present study assessed whether pre-pubertal GX would influence ethanol/stress interactions, or responsiveness to ethanol in a social setting. Again, we found little impact of GX on ethanol sensitivity in animals of either sex under these circumstances.…”

“…The former but not the latter effect was evident in the current study. It is possible that use of a broader dose-response curve may have revealed GX-related alterations in ethanol effects on social behavior, although a similar lack of GX effects on social behavior (albeit in the absence of stress challenge) was seen when assessing low, moderate and high doses of ethanol in late adolescence (Morales et al, 2014b). …”

Estrogen Modulates Ethanol‐Induced Memory Deficit in Postpubertal Adolescent Rats

“…Thus, postpubertal gonadectomy eliminated EtOH‐induced memory impairment in female rats. It has been reported that acute EtOH treatment in female rats subjected to pre pubertal ovariectomy does not alter social behavior (Morales et al., ). The difference in findings between that study and the present study could be due to several factors.…”