Longitudinal Examination of Learning and Memory in Rats Following Adolescent Exposure to 3,4-Methylenedioxymethamphetamine or 5-Methoxy-N,N-Diisopropyltryptamine

Abstract

A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown about the neurobiological consequences of Foxy use. In addition, research into the long-term neuropsychological repercussions associated with these two compounds remains incomplete. The goal of the present research was to explore the effects of MDMA or Foxy on cognitive processes associated with adolescent exposure considered over much of the lifespan. Here we investigated whether the reported effects following adolescent exposure resolved in early adulthood or continued throughout life. The protocol involved repeated doses of either MDMA or Foxy during the period defined as mid-adolescence (postnatal days 34 - 46) in rats, followed by the use of four series of learning and memory tasks repeated at different points in the rodent lifespan. At four time points in adulthood, the animals were trained and tested on a on a series of spatial and non-spatial memory tasks designed to assess the impact and severity of Foxy and MDMA. Oddly, MDMA-treated rats were impaired on a step down passive avoidance task. The performance of the drug-treated rats was markedly inferior to that of the control animals on more demanding water maze tasks, with some results suggesting a lack of flexibility in adapting to changing task demands. MDMA rats were the most impaired. While some persistent cognitive deficits were found, no significant group differences in serotonin or dopamine levels were found in any of the measured regions of the brain changes, cortical or subcortical. These results provide evidence for compromised neurocognition that continues long after drug exposure in the absence of any discernable changes in neurotransmitter levels. Several possible physiological and neurochemical mechanisms associated with these compounds requiring further study are also outlined.