The Effects of Adolescent Methamphetamine Exposure on Depression-Like Behavior and the Hypothalamic Vasopressin System in Late Adolescent and Adult Mice
Methamphetamine (meth) is a highly addictive and powerful psychomotor stimulant that affects the central nervous system by increasing synaptic levels of the neurotransmitter dopamine in the brain. Meth is known to have neurotoxic effects in the adult brain that can lead to behavioral and cognitive deficits. However, little research has examined the effects of meth on the adolescent brain, which is concerning as the use of meth among adolescents is increasing. Thus we were interested in examining the long-term effects of early adolescent meth use on behavior, cognition, and the vasopressin system in the hypothalamus, which is associated with the stress response.
Mice were administered a binge dose of meth or saline over a 2-day period during early adolescence. Mice were then randomly separated into 2 groups, with half being tested in late adolescence and half being tested in adulthood. Mice underwent the open field test (test of locomotor activity and anxiety-like behavior), the novel object recognition test (test of object memory), the social interaction test, the Porsolt forced swim test (test of depression-like behavior), and the Morris water maze test (test of spatial memory). Vasopressin immunohistochemistry was performed in the paraventricular nucleus of the hypothalamus to quantify vasopressin producing cells.
The results showed that mice exposed to meth spent significantly more time immobile during the Porsolt forced swim test, which implies increased depression-like behavior, both in late adolescence and adulthood. This effect of meth on depression-like behavior was most pronounced by the late adolescent male mice, suggesting younger male mice are more susceptible to the behavioral effects of adolescent meth exposure. Similarly, late adolescent meth-exposed male mice showed fewer vasopressin-positive cells in the paraventricular nucleus compared to late adolescent saline-exposed male mice, and the decrease in vasopressin-positive cells correlated with increased depression-like behavior in the Porsolt forced swim test among the male mice.
These results suggest that adolescent meth exposure can increase depression-like behavior, especially among male mice, and that this increase in depression-like behavior may be caused by meth-induced decreases in vasopressin-positive cells and alterations in the stress response system. These results correspond well with findings in human adolescent meth users, who show increased rates of depression and suicide ideation compared to adolescents using other drugs.
The findings from this study were presented by Sewanee undergraduate student Lauren Joca and Dr. Jessica Siegel at the Society for Neuroscience conference in November 2012 in New Orleans. The paper has been published in Developmental Neuroscience.