Developmental striatal critical period of activity-dependent plasticity is also a window of susceptibility for haloperidol induced adult motor alterations

Abstract

Experience-dependent plasticity during critical periods of postnatal (PN) development shapes the adult brain anatomy and function. In rat motor system, there is a critical period of activity-dependent plasticity in the striatum (PN30-37). In this period, motor activity of running in a circular path induced in the Circling Training test (CT), elicits several plasticity changes on striatal synapses. It has been recently proposed that developmental critical periods might represent a unique pharmacological window of vulnerability to induce life-lasting behavioral modifications. In this paper we tested the hypothesis of existence of a pharmacological susceptibility to induce adult alterations on motor behavior during the striatal critical period. Due to its main action on the striatum and developmental motor behavioral effects, we applied the prototypical antipsychotic haloperidol to male rats (i.p. 0.7 or 2.5 mg/kg/day) before, during or after the period of plasticity (PN20-27, PN30-37 or PN40-47 respectively). Then, in the adulthood (PN80), we evaluated induced motor activity in the CT. The results showed that only rats exposed to the D2R blocker during the period PN30-37 increased the CT activity in comparison to control rats. Moreover, only these animals also showed an increase in the spontaneous locomotor activity at the open field test. These behavioral alterations were not accompanied by permanent striatal changes either on the number of D2R binding sites or on its mRNA expression levels. In conclusion, we have shown a pharmacological susceptibility of inducing adult motor behavior alterations by haloperidol during a natural critical period of activity-dependent plasticity (PN30-37) in rat striatum development. These results also emphasize the importance of behavioral screening for pharmacological agents to be used in developmental stages of maturation.