IMPACT OF ADOLESCENT INTERMITTENT ETHANOL EXPOSURE IN MALE AND FEMALE RATS ON SOCIAL DRINKING AND NEUROPEPTIDE GENE EXPRESSION

Background: Alcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety-like alterations and enhanced sensitivity to ethanol-induced social facilitation following adolescent intermittent ethanol (AIE) exposure. These consequences of AIE may influence adult social drinking in a sex-specific manner. Methods: To test effects of AIE on social drinking, male and female Sprague-Dawley rats exposed to water or ethanol [0 or 4 g/kg, intragastrically, every other day, between postnatal day (P) 25 and 45] were tested as adults (P72-83) in a social drinking paradigm (30-minute access to a 10% ethanol solution in supersac or supersac alone in groups of three same-sex littermates across two 4-day cycles separated by 4 days off). Social behavior was assessed during the last drinking session, with further assessment of oxytocin (OXT), oxytocin receptor (OXTR), vasopressin (AVP) and vasopressin receptors 1a and 1b (AVPR1a, AVPR1b) in the hypothalamus and lateral septum. Results: Males exposed to AIE consumed more ethanol than water-exposed controls during the second drinking cycle, whereas AIE did not affect supersac intake in males. AIE-exposed females consumed less ethanol and more supersac than water-exposed controls. Water-exposed females drinking ethanol showed more social investigation as well as significantly higher hypothalamic OXTR, AVP, and AVPR1b gene expression than their counterparts ingesting supersac and AIE females drinking ethanol. In males, hypothalamic AVPR1b gene expression was affected by drinking solution, with significantly higher expression evident in males drinking ethanol than those consuming supersac. Conclusions: Collectively, these findings provide new evidence regarding sex-specific effects of AIE on social drinking and suggest that the hypothalamic OXT and AVP systems are implicated in the effects of ingested ethanol on social behavior in a sex- and adolescent exposure-dependent manner.

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

ABSTRACTBackgroundIn male rats, physical contexts that are associated with alcohol can invigorate responding to a discrete, alcohol-predictive conditioned stimulus (CS), and amplify priming-induced reinstatement. Here, we examined these effects as a function of biological sex.MethodsMale and female Long-Evans rats were acclimated to drinking ethanol (EtOH, 15% v/v) in their home cages. Next, they were trained to associate an auditory CS (10 s; white noise; 15 trials per session) with EtOH delivery (0.2 ml per CS; 3.0 ml per session) into a fluid port for oral intake. Training occurred in a distinctive context containing specific visual, olfactory, and tactile stimuli. During alternating sessions rats were exposed to a second context where they did not receive EtOH. At test, CS presentations occurred in both contexts without EtOH delivery. Rats then underwent extinction using repeated unreinforced presentations of the CS in both contexts. An alcohol-primed reinstatement test was then conducted, in which 0.2 ml of EtOH was presented both at the start of the session and during the first CS presentation, after which no EtOH was delivered for the remainder of the session.ResultsAt both test and reinstatement, male rats made significantly more CS port-entries in the context associated with alcohol delivery than in the context in which alcohol was never experienced. Unlike males, female rats made a similar number of CS port-entries at test in both the alcohol context and the neutral context. The reinstatement observed in female rats was not affected by context.ConclusionsThese findings identify novel sex differences in the capacity of an alcohol-associated context to modulate responding to a discrete, alcohol-predictive cue.

Inhibition of the Ventral Hippocampus Increases Alcohol Drinking

The function of the ventral hippocampus (vHC) supports many behaviors, including those related to reward seeking behaviors and drug addiction. We used a mouse model of alcohol dependence and relapse to investigate the role of the vHC in alcohol (ethanol) drinking. One experiment used a chemogenetic approach to inhibit vHC function while ethanol dependent and non-dependent mice had access to ethanol. Interestingly, the non-dependent mice expressing an inhibitory DREADD in the VHC showed a significant increase in ethanol drinking (∼30%) after hM4Di DREADD activation with clozapine-n-oxide (CNO; 3 mg/kg, ip.) compared to vehicle. On the other hand, ethanol dependent mice, which were already drinking significantly more ethanol than non-dependent mice, only had a slight, non-significant increase in drinking after CNO challenge. In a separate group of dependent and non-dependent mice, GCaMP6f calcium-dependent activity was recorded in the vHC while mice were actively drinking ethanol. These data showed that once mice were rendered ethanol dependent and were drinking more ethanol than the non-dependent mice, calcium signaling in the ventral hippocampus decreased (∼45%) in the ethanol dependent mice compared to the non-dependent mice. Together, these findings suggest that ethanol dependence reduces activity of the ventral hippocampus and that reduced function of this brain region contributes to increased ethanol drinking.

Behavior of sheep drinking ethanol solution

Sheep that were habituated to drinking 10% (vol/vol) ethanol solution instead of water were subjected to proven thirst stimuli to study the effect of chronic ethanol intake on brain mechanisms subserving thirst. Sheep that had not previously drunk 10% ethanol were also tested. All sheep were trained to press a pedal that delivered 50 ml/press of fluid (either 10% ethanol or water) into a drinking cup. In some experiments, fluids were presented in bins. All animals had access to only one fluid at a time. Five ethanol-drinking sheep appeared healthy and maintained body weight over 18 mo. They always preferred water to 10% ethanol. The intracerebroventricular (icv) infusion of angiotensin II (ANG II) at 3.8 micrograms/h for 2 h increased ethanol intake from 15 +/- 10 to 200 +/- 55 ml in the 1st h, but 2,850 +/- 320 ml of water was drunk in the 2nd h. The icv infusion of 500 mM NaCl had a similar effect. After fluid deprivation for 22 or 46 h, ethanol intake in 1 h of access was only 280 +/- 40 and 400 +/- 90 ml, respectively, and 24-h intake was not increased. Water-drinking sheep drank 1,300 +/- 195 ml of water in 1 h after 22-h water deprivation, and 24-h intake was 1.5 times normal. The icv infusion of ANG II in these sheep increased water intake in 1 h from 10 +/- 10 to 1,630 +/- 250 ml and intake of 10% ethanol to only 310 +/- 60 ml. In conclusion, sheep accept 10% ethanol as a substitute for water for daily drinking.(ABSTRACT TRUNCATED AT 250 WORDS)