Female Sprague-Dawley rats display greater appetitive and consummatory responses to alcohol

Abstract

The narrowing of the gender gap in alcohol drinking patterns is a concern because women are more susceptible to adverse health consequences of alcohol use. Animal models of alcohol-seeking and –consuming are useful to delineate sex differences to test for effective sex-specific pharmacological treatments. We investigated potential sex differences in appetitive and consummatory responses to alcohol. Appetitive behaviors included numbers of head entries into the dipper access area and active lever presses. Consummatory behaviors included number of reinforcers delivered and consumed. Male and female Sprague-Dawley rats were placed on an overnight alcohol (10%) drinking schedule and trained to lever press for alcohol (10% solution). Separate groups of male and female animals had access to water overnight and were trained to lever press for sucrose (3% solution). Tests were conducted under a progressive ratio schedule of reinforcement. Alcohol-responding females demonstrated higher alcohol intake overnight and showed greater appetitive and consummatory responses compared to males. Similar sex differences were seen in the sucrose group. Effect sizes indicated greater sex differences in consummatory measures in the alcohol vs. sucrose groups. Conversely, greater sex differences in appetitive behaviors were observed in the sucrose vs. alcohol groups. Overall, the magnitude of the sex differences was stronger for appetitive behaviors compared to consummatory behaviors. Findings of quantitative sex differences in appetitive and consummatory behaviors for alcohol and for the natural reinforcer, sucrose, suggest this procedure is useful to assess efficacy of sex-specific treatments aimed at reducing appetitive and consummatory responses to alcohol.

Early life stress and the propensity to develop addictive behaviors

“…We saw this when we first ran female rats in operant cocaine self‐administration and published on some of these sex differences (Kosten and Zhang, 2008). We also see sex differences in operant alcohol self‐administration responses (Nieto and Kosten, 2017). Chronic stress experienced in adulthood (Wood and Shors, 1998) or early in life (Kosten et al, 2005a) has sex‐dependent effects on fear conditioning.…”

Sex Differences in the Neurobiology of Alcohol Use Disorder

“… 37 , 38 Female rats show more appetitive approach, measured by the total number of head entries into a dipper access area (dipper approaches) and have higher levels of lever presses (active lever approaches) to obtain the alcohol reward. 39 Consummatory behavior, measured by the number of dipper presentations into the access area (reinforcers delivered) is also higher in female rats compared to male rats. 39 This is consistent with other rodent studies showing that females consume more alcohol relative to body weight and engage in higher levels of cue-mediated alcohol-seeking behaviors compared to males.…”

“… 39 Consummatory behavior, measured by the number of dipper presentations into the access area (reinforcers delivered) is also higher in female rats compared to male rats. 39 This is consistent with other rodent studies showing that females consume more alcohol relative to body weight and engage in higher levels of cue-mediated alcohol-seeking behaviors compared to males. 40 – 42 …”

“…The mesocorticolimbic dopamine pathway may contribute to sex differences in appetitive and consummatory behaviors, given its essential role in conditioning and associative learning of environmental and physiological cues that predict alcohol reward availability. 39 , 43 – 45 Alcohol binge drinking activates cells in the ventral tegmental area (VTA) of the mesocorticolimbic dopamine pathway. 45 – 47 This midbrain structure is the origin of dopaminergic cells that project to the ventral striatum (nucleus accumbens), frontal cortex, and amygdala.…”

Sex differences in the amplification of responding to an alcohol-predictive cue by an alcohol-associated context

“…Previous findings of females acquiring and retaining associations more effectively than males have been shown in associative learning paradigms (Dalla and Shors, 2009). Females have also been shown to make more entries into a dipper containing alcohol compared to males during operant self-administration (Nieto and Kosten, 2017). Notably the total durations of CS port-entries and the latency to produce CS port-entries did not differ across sex, suggesting that both males and females were equally motivated to make port-entries during the CS.…”