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

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.