Periadolescent oral manganese exposure affects conditioned place preference by cocaine and conditioned place aversion by lithium chloride in rats

Abstract

Manganese neurotoxicity compromises basal ganglia functions that could affect the limbic system and drug sensitivity. Male rats were orally exposed to manganese chloride (0, 100, 200 mg/kg/day Mn) for 15 days starting at postnatal day (PND) 28. In Experiment 1, conditioned place preference (CPP) was conducted in a two-compartment apparatus in which cocaine was paired with the least-preferred compartment as determined by a pretest. Animals received 0, 2.5, or 5 mg/kg cocaine HCl (i.p.) for 4 days and, alternatively, vehicle-only for 4 days. Animals exposed to 0 mg/kg/day Mn showed an increased place preference for 2.5 mg/kg cocaine and a reduced place preference for 5 mg/kg cocaine. In contrast, animals exposed to 100 mg/kg/day Mn showed an increased place preference for both 2.5 and 5 mg/kg cocaine, and animals exposed to 200 mg/kg/day Mn showed an increased place preference for 5 mg/kg cocaine only. To determine the possible effects of alterations of learning mechanisms by manganese, a conditioned place aversion (CPA) procedure was employed for Experiment 2. Animals received 40 mg/kg lithium chloride (i.p.) for 4 days, and alternatively, vehicle-only for 4 days. Animals exposed to 100 mg/kg/day Mn and 200 mg/kg/day Mn showed an increased place aversion for 40 mg/kg LiCl when compared to animals exposed to 0 mg/kg/day Mn. However, the increase was not statistically significant. These findings are discussed within a framework of possible manganese-induced disturbance of neurochemical function relating to drug reward and learning.