Patterns matter: continuous Vs intermittent access to ethanol differently affects withdrawal behavioural phenotype and maternal care in female rats.

Abstract

Modeling voluntary ethanol consumption in female rats is crucial for gaining further insight in gender-related vulnerability to alcohol. Since ethanol effects depend not only on the amount consumed, but also on drinking pattern, this study aimed at assessing the influence of continuous and intermittent ethanol self-administration on peculiar aspects of female behavioural repertoire during withdrawal and relapse. Female rats undergoing a 15-week-long, 20% ethanol continuous or intermittent (3days/week) access, respectively named CARs and IARs, were tested for alcohol intake (gr/kg) and preference. During withdrawal we assessed: novelty and reward preference in novel object exploration and saccharin tests; depressive-like behaviour in forced-swim test; anxiety-like behaviour in EPM; behavioural reactivity in Open Field. Female rats reinstated ethanol intake from the second pregnancy week and maternal behaviour was assessed by scoring retrievals, nursing, pup care, dam self-care and non-maternal behaviours. Along the paradigm, IARs displayed higher ethanol preference and intake than CARs (p<0.001). IARs' ethanol intake decreased during pregnancy, with respect to pre-pregnancy basal level (p<0.001) and to CARs' (p<0.01; p<0.05), and increased for both groups immediately after delivery, with respect to respective pre-pregnancy basal levels (p<0.01; p<0.05). During forced abstinence, both groups displayed lower novelty and saccharin preference (p<0.01; p<0.05), with IARs displaying lower saccharin preference with respect to CARs (p<0.001). Both groups showed increased immobility in forced-swim test (p<0.01), CARs reduced open arm time and entries in EPM (p<0.05), while IARs increased central preference in Open Field (p<0.05), with respect to controls. After delivery, IARs significantly decreased all maternal care-related behaviours with respect to controls (p<0.01). Our data indicate that heavy intermittent pattern of ethanol administration induces marked neuroadaptive alterations in the reward and affectivity pathways, able to induce depressive- and anhedonic-like states, and detrimental effects on highly conserved behaviours, such as maternal care.