Withdrawal induces distinct patterns of FosB/∆FosB expression in outbred Swiss mice classified as susceptible and resistant to ethanol-induced locomotor sensitization

Abstract

Chronic drug exposure and drug withdrawal induce expressive neuronal plasticity which could be considered as both functional and pathological responses. It is well established that neuronal plasticity in the limbic system plays a pivotal role in relapse as well as in compulsive characteristics of drug addiction. Although increases in FosB/DeltaFosB expression constitute one of the most important forms of neuronal plasticity in drug addiction, it is unclear whether they represent functional or pathological plasticity. It is of noteworthy importance the individual differences in the transition from recreational use to drug addiction. These differences have been reported in studies involving the ethanol-induced locomotor sensitization paradigm. In the present study we investigated whether sensitized and non-sensitized mice differ in terms of FosB/DeltaFosB expression. Adult male outbred Swiss mice were daily treated with ethanol or saline for 21days. According to the locomotor activity in the acquisition phase, they were classified as sensitized (EtOH_High) or non-sensitized (EtOH_Low). After 18h or 5days, their brains were processed for FosB/DeltaFosB immunohistochemistry. On the 5th day of withdrawal, we could observe increased FosB/DeltaFosB expression in the EtOH_High group (in the motor cortex), in the EtOH_Low group (in the ventral tegmental area), and in both groups (in the striatum). Differences were more consistent in the EtOH_Low group. Therefore, behavioral variability observed in the acquisition phase of ethanol-induced locomotor sensitization was accompanied by differential neuronal plasticity during withdrawal period. Furthermore, distinct patterns of FosB/DeltaFosB expression detected in sensitized and non-sensitized mice seem to be more related to withdrawal period rather than to chronic drug exposure. Finally, increases in FosB/DeltaFosB expression during withdrawal period could be considered as being due to both functional and pathological plasticity.