The behavioural implications of postnatal exposure to benzylpiperazhie and methamphetamine - a longitudinal doserelated study in male and female rats.

摘要

Despite worldwide concern about the consumption of psychoactive substances during earlier development, the long-term behavioural effects of many have remained largely unexplored. By the mid 2000’s there was a public epidemic declared on the escalating rate of individuals consuming New Zealand’s form of methamphetamine (MA), called ‘P’ (short for 'pure' methamphetamine). Within this environment the emergence of new unregulated psychoactive compounds appeared. These were known and marketed as “legal or herbal highs’. N-benzylpiperazine (BZP) became the main ingredient in the legal highs and was marketed as a safe alternative to “P”, however there was no research to support this claim. The present study investigated the long-lasting effects on anxiety-like behaviour in rats, after BZP or MA administration during early to late adolescent development, examining variables: drug; age; sex; dose; and whether differences remained over time. Rats were either administered saline, BZP (5.0, 10.0, or 20.0 mg/kg) or MA (0.5, 1.0, 2.0 mg/kg) at three different ages of adolescence (Post Natal Day [PND]: PND31-40, PND41-50, PND51-60) for a period of ten days. After a thirty day wash-out period rats were tested in four different rodent tests of anxiety: Y-maze, Elevated Plus Maze, Light/dark Emergence Box and a Social Interaction Test. Behavioural testing occurred again at PND 120 and PND 200 to assess behavioural change over time. Daily BZP or MA treatment across the three different ages of adolescence increased anxiety-like behaviours in all behavioural measures and this was maintained over time. In summary, rats treated with BZP or MA during PND31-40 and PND41-50 displayed more anxiety-related behaviour comparative to control rats and this effect increased with drug dose, primarily for male-treated rats. The general pattern of results was more complex for PND51-60 treated rats, with MA-treated female rats displaying increased anxiety-like behaviours as the dose of MA increased and rats treated with the highest dose of BZP displaying decreased emotionality. There were more similarities between BZP and MA than differences, yet adolescent BZP treatment appeared to have greater impact on adult behaviour than adolescent MA treatment. Additionally, male rats exposed to both BZP and MA displayed increased anxiety-like behaviours compared to female-treated rats. The implications are far reaching, as there is currently a cohort of the population that consumed BZP legally as adolescents who may have a greater risk for the development of increased anxiety with developing age. In sum, the effect of adolescent exposure to psychostimulant drugs affected anxiety-like behaviours that were observable into middle adulthood, suggesting that the vulnerability to anxiety may be shaped by drug use in adolescence.