Maternal separation fails to render animals more susceptible to methamphetamine-induced conditioned place preference

Abstract

The maternal separation (MS) paradigm is an animal model that has been successfully used to study the long term effects of child abuse and neglect. Experiments showed that animals subjected to trauma and stress early in life display behavioural, endocrinological and growth factor abnormalities at a later stage in life, results that mirrored clinical conditions. It is apparent that adverse events early in life may affect the development and maturation of the brain negatively. The purpose of the present study was to investigate whether the abnormal brain development occurring in separated animals would also enhance the development of a preference for psychostimulant drug usage. Rats were subjected to maternal deprivation and further exposed to methamphetamine-induced conditioned place preference (CPP) which primarily measures drug reward (ventral striatum) learning and memory. Apomorphine-induced locomotor activity was also assessed to investigate the effects of methamphetamine on the dorsal (primarily locomotor activity) striatal dopaminergic system. We found that four consecutive injections of methamphetamine resulted in CPP behaviour 24 h after the 4th injection. A further four injections yielded similar CPP results and this effect lasted for at least 7 days until the third CPP assessment. These animals also had decreased ACTH and corticosterone secretions, but the prolactin levels were increased. Prior exposure to maternal separation did not have any effect on the CPP test. The ACTH and corticosterone secretions were also similarly reduced. However maternal separation decreased the release of prolactin and this reduction was not evident in the separated group that received methamphetamine. There was no significant difference in the apomorphine-induced locomotor activity of normally reared animals whether they received methamphetamine or saline. Interestingly there was a significant difference in locomotor activity between the two groups of animals that were subjected to maternal deprivation. The separated animals that received methamphetamine displayed markedly reduced locomotor activity upon apomorphine administration when compared to those that were treated with saline. Taken together, we conclude that maternal deprivation differentially influences dorsal and ventral striatal regions implicating dopaminergic mechanisms.