Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats

Abstract

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol s aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0 g/kg ethanol in a binge-like pattern during postnatal days (PD) 35–45. In adulthood (> PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5 g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females.

Sex differences in adult Wistar rats in the voluntary consumption of ethanol after pre-exposure to ethanol-induced flavor avoidance learning

“…After three pairings of the CSa and 1.5 g/kg ethanol, males were consuming 94.1% less CSa than they were at baseline; females were consuming 68.9% less (see Table 1). These results are consistent with those obtained by several other research groups (Caihol and Mormede, 2002;Morales et al, 2014;Schramm-Sapyta et al, 2014;Sherrill et al, 2011a). In fact, a relative sensitivity of males as compared to females with this preparation is generally reported, although the strength of the sex difference varies across studies and is dependent upon a number of factors (see Busse et al, 2005).…”

“…The results of our experiments could indicate, on the one hand, that the enhanced sensitivity of male rats to ethanol-induced aversion (experiment 1), may contribute to their reduced voluntary ethanol intake behavior (non-experienced males of experiment 2; Cacace et al, 2011;Doremus et al, 2005;Sherrill et al, 2011aSherrill et al, , 2011bTruxell et al, 2007;Vetter-O'Hagen et al, 2009;Vetter-O'Hagen and Spear, 2011). Consistent with this notion, previous studies have demonstrated an inverse relationship between ethanol self-administration and ethanol-induced FAL, though this may be strain dependent (reviewed in Sherrill et al, 2011a).…”

“…In fact, a relative sensitivity of males as compared to females with this preparation is generally reported, although the strength of the sex difference varies across studies and is dependent upon a number of factors (see Busse et al, 2005). While Sherrill et al (2011a) review and discuss several factors that could contribute to the enhanced sensitivity of males to ethanolinduced FAL (such as possible differences between males and females in sensitivity to the aversive effects of ethanol, and cognitive or metabolic differences), the data thus far collected is too inconsistent to allow for definitive conclusions. Some studies have found no differences at all between males and females to the aversive effects of ethanol (Morales and Spear, 2013;Vetter-O'Hagen et al, 2009).…”

“…One factor that has received considerable attention is the sex of the subject used in the FAL procedure. Sex differences in FAL have been examined with a variety of compounds such as lithium chloride (LiCl) (Chambers et al, 1981;Dacanay et al, 1984), cocaine (Busse et al, 2005;Jones et al, 2006) and ethanol (Caihol and Mormede, 2002;Morales et al, 2014;Schramm-Sapyta et al, 2014;Sherrill et al, 2011a). The relative sensitivity of males (compared to females) within this preparation is generally reported, although the strength of the sex difference varies across studies and is dependent upon a number of factors (see Busse et al, 2005).…”

“…Both sexes were included given that, despite evidence for sex differences in ethanol consumption (Blanchard et al, 1993;Doremus et al, 2005;Lancaster et al, 1996), relatively few studies have examined potential sex differences in the emergence of tolerance or sensitization to ethanol, and among those that have, the findings are mixed (Caihol and Mormede, 2002;Linsenbardt et al, 2009;Morales et al, 2011;Sherrill et al, 2011a;Webb et al, 2002). In fact, the conditions under which the stimulus properties of ethanol change with repeated exposure are not well defined, especially with regard to differences in male vs female responses to repeated exposure to ethanol.…”