Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327 does not prevent acquisition, expression, and extinction of ethanol-seeking behavior in mice

Although extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of a variety of associative learning tasks, its involvement in the acquisition and extinction of ethanol (EtOH)-induced conditioned place preference (CPP) remains unknown. Therefore, in these experiments we examined the effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP extinction. The parametric findings of Experiment 1 showed that three 30-min (but not 15- or 5-min) non-reinforced trials were required to completely extinguish EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50 mg/kg), administered 30 or 90 min prior to extinction trials, was unable to impair EtOH-CPP extinction. Experiment 4 showed that SL327 (50 mg/kg) had no effect on acquisition of EtOH-CPP or the development of EtOH-induced sensitization during conditioning. When administered prior to testing in Experiments 5 and 6, SL327 did not alter expression of EtOH-CPP but did reduce test activity. Importantly, SL327 significantly reduced pERK protein levels when assessed in the dorsal striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH-related learning and EtOH reward in mice, as assessed with CPP, are not impaired by the systemically administered MEK-inhibitor SL327.

Research highlights▶ Extinction of ethanol-CPP depends on trial duration. ▶ SL327 does not impair acquisition, expression, and extinction of ethanol-CPP. ▶ SL327 suppresses locomotor activity but does not prevent EtOH-induced sensitization. ▶ Systemic SL327 reduces pERK protein levels in dorsal striatum and motor cortex.