Effects of environmental enrichment on nicotine-induced sensitization and cross-sensitization to d-amphetamine in rats

Introduction: Research indicates that adolescent nicotine exposure may predispose individuals to use other psychostimulants later in adulthood, offering support for the incentive-sensitization theory of addiction. Preclinical studies testing the incentive-sensitization theory show that repeated nicotine exposure in adolescent rats can lead to an increased sensitivity to the motor stimulant effects of nicotine and other psychostimulants in adulthood. Although previous nicotine exposure can increase sensitivity to stimulant drugs, rats raised in enriched conditions (EC) show, decreased sensitivity to psychostimulant drugs compared to rats raised in isolation conditions (IC). Methods: We examined whether nicotine sensitization or cross-sensitization to d-amphetamine induced by adolescent nicotine exposure is altered by exposure to environmental enrichment. Adolescent EC and IC male rats received subcutaneous (s.c.) injections of saline or 0.4. mg/kg of nicotine once daily for seven days. Thirty-five days following the last nicotine injection EC and IC animals were challenged with saline, nicotine (0.2 or 0.4. mg/kg) or d-amphetamine (0.5 or 1.0. mg/kg). Results: EC rats failed to show nicotine sensitization at either nicotine dose tested while IC rats showed nicotine sensitization following the 0.4. mg/kg nicotine dose. EC rats also failed to show nicotine-induced cross-sensitization to the 0.5. mg/kg dose of d-amphetamine while IC rats displayed cross-sensitization. However, EC rats did exhibit nicotine-induced cross-sensitization to the 1.0. mg/kg dose of d-amphetamine. Conclusion: These findings indicate that environmental enrichment can alter the ability of adolescent nicotine exposure to induce sensitization and cross-sensitization in adulthood and may be used as a protectant factor against adolescent nicotine exposure.