Social defeat in adolescent mice increases vulnerability to alcohol consumption

Abstract

This study employs an oral operant conditioning paradigm to evaluate the effects of repeated social defeat during adolescence on the reinforcing and motivational actions of ethanol in adult OF1 mice. Social interaction, emotional and cognitive behavioral aspects were also analyzed, and real-time polymerase chain reaction (PCR) experiments were performed to study gene expression changes in the mesocorticolimbic and hypothalamus-hypophysis-adrenal (HHA) axis. Social defeat did not alter anxiety-like behavior in the elevated plus maze or cognitive performance in the passive avoidance and Hebb-Williams tests. A social interaction test revealed depression-like symptoms and social subordination behavior in defeated OF1 mice. Interestingly, social defeat in adolescence significantly increased the number of effective responses, ethanol consumption values and motivation to drink. Finally, real-time PCR analyses revealed that social defeat significantly increased tyrosine hydroxylase and corticotropin-releasing hormone in the ventral tegmental area and paraventricular nucleus, respectively. In contrast, mu-opioid receptor gene expression was decreased in the nucleus accumbens of socially defeated mice. In summary, these findings suggest that exposure to social defeat during adolescence increases vulnerability to the rewarding effects of ethanol without affecting emotional or cognitive performance. The gene expression alterations we have observed in the mesocorticolimbic and HHA axis systems of defeated mice could be related with their increased ethanol consumption. These results endorse future research into pharmacological strategies that modulate these systems for the treatment of social stress-related alcohol consumption problems.

Peripubertal stress of male, but not female rats increases morphine‐induced conditioned place preference and locomotion in adulthood

“…Conversely, morphine acts on μ‐opioid receptors, which are expressed on inhibitory GABAergic interneurons of the ventral tegmental area, leading to strong inhibition of GABA neurons and disinhibition of dopamine neurons (Luscher & Ungless, ). Previous studies also show that social defeat stress in adolescence increased amphetamine or cocaine‐induced CPP (Burke et al, ; Rodriguez‐Arias et al, ). Our result is consistent with these studies and suggested that non‐social stress and social stress may have a similar effect on animals’ vulnerability to drug abuse in adulthood.…”

“…For example, Burke, Watt, and Forster (2011) reported that rats exposed to repeated social defeat in adolescence (P35-P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70) (Burke et al, 2011). Also, Rodriguez-Arias et al (2016) found that social defeat in adolescence significantly increased ethanol consumption and motivation to drink (Rodriguez-Arias et al, 2016). Regarding the non-social stressors, some studies find that they could also enhance vulnerability to drug addiction (Watt et al, 2017).…”

Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice

“…The relationship between stress and ethanol drinking is complex and several variables including type of stress, strain, sex, and time course can ultimately influence the direction and magnitude of ethanol-drinking behavior (Spanagel, Noori, & Heilig, 2014). Future experiments will aim to validate and employ a specific model for stress-escalated ethanol drinking, such as chronic stress preceding ethanol consumption (Lopez, Doremus-Fitzwater, & Becker, 2011; Rodriguez-Arias et al, 2014). …”

Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress

“…For example, insufficient mPFC dopamine activity during reward processing is associated with both increased impulsive choice (Yates et al, 2014) and perseveration in conditioned response despite changes in reward contingency (Floresco, 2013). In accordance with this, rats defeated in adolescence show enhanced preference for psychostimulantassociated cues even when the drug is no longer available (Burke et al, 2011;Rodriguez-Arias et al, 2017), along with greater alcohol and cocaine self-administration (Burke & Miczek, 2015;Rodriguez-Arias et al, 2017;Rodríguez-Arias et al, 2017). Findings from the current and previous studies suggest that targeting D2 autoreceptors along with DAT to restore dopamine availability in the mPFC could lead to more efficacious treatment of the cognitive deficits seen in adult neuropsychiatric disorders promoted by periadolescent stress (Watt et al, 2017).…”