Acute and chronic ethanol differentially modify the emotional significance of a novel environment: implications for addiction

Abstract

Using open-field behaviour as an experimental paradigm, we demonstrated a complex interaction between the rewarding/stimulating effects and the anxiogenic/stressful effects of both novelty and acute or chronic amphetamine in mice. As a consequence of this interaction, acute amphetamine-induced hyperlocomotion was inhibited, whereas the expression of its sensitization was facilitated in a novel environment. In the present study, we aimed to investigate the interactions between exposure to a novel environment and the acute and chronic effects of ethanol (Eth), a drug of abuse known to produce anxiolytic-like behaviour in mice. Previously habituated and non-habituated male Swiss mice (3 months old) were tested in an open field after receiving an acute injection of Eth or following repeated treatment with Eth. Acute Eth administration increased locomotion with a greater magnitude in mice exposed to the apparatus for the first time, and this was thought to be related to the attenuation of the stressful effects of novelty produced by the anxiolytic-like effect of acute Eth, leading to a subsequent prevalence of its stimulant effects. However, locomotor sensitization produced by repeated Eth administration was expressed only in the previously explored environment. This result might be related to the well-known tolerance of Eth-induced anxiolytic-like behaviour following repeated treatment, which would restore the anxiogenic effect of novelty. Our data suggest that a complex and plastic interaction between the emotional and motivational properties of novelty and drugs of abuse can critically modify the behavioural expression of addiction-related mechanisms.

Chronic alcohol exposure differentially affects activation of female locus coeruleus neurons and the subcellular distribution of corticotropin releasing factor receptors

“…However, over the course of chronic administration, it is hypothesized that desensitization to the anxioloytic effects of ethanol occurs, resulting in a transition to anxiety-like behaviors (King et al 2006). Consistent with this, Fukushiro et al described an increase in locomotion following administration of acute ethanol compared with a decrease in exploratory behaviors after chronic administration (Fukushiro et al 2012). In the present study, ethanol-treated animals spent less time engaged in all three measured exploratory behaviors in the EZM: time in the open arms, head dips, and standing, when compared to their control counterparts.…”

Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats

“…Karayadian and coworkers [6] considered that decreases in the number of line crossings and rearings in the OF represented behavioral signs of anxiety during ethanol withdrawal. Fukushiro and others [7] assessed the acute and chronic effects of ethanol on OF behavior in mice. They found an enhancement of motor activity following acute ethanol administration, a result that was reported as proof of the ethanol-induced reduction of the aversive effect of the novel environment (i.e., an anxiolytic effect).…”

Alcohol-induced dysregulation of stress-related circuitry: The search for novel targets and implications for interventions across the sexes

“…Acevedo et al (2014) also noted increased anxiolytic effects of acute ethanol in rats in the EZM at multiple ethanol doses (Acevedo et al, 2014). In contrast, Fukushiro et al described an increase in locomotion following administration of acute ethanol compared with a decrease in exploratory behaviors after chronic administration, indicating a switch to anxiogenesis (Fukushiro, Josino, 2012). In agreement with the work by Fukushiro et al and expanding upon it, a recent study by our lab examined behaviors in the EZM in both sexes after chronic ethanol exposure.…”

“…For example, affective disorders and many anxiety disorders are nearly twice as prevalent in females compared to males (Fukushiro et al, 2012, Kessler et al, 1994). The NIAAA states that 5.3 million women in the United States use alcohol in a way that “threatens their health, safety and general well-being,” and that in addition, the problems that plague women drinkers are equal to, or greater than, those that affect men (Alcoholism, 2008).…”