Methadone does not alter key parameters of adult hippocampal neurogenesis in the heroin-naïve rat

Abstract

Methadone is a synthetic opiate that is useful in a variety of clinical settings, including in maintenance therapy of heroin dependence and as an analgesic. However, methadone can have negative effects on cognition in humans and in rodents. The mechanisms underlying methadone-induced disruption in cognition are unknown. One possibility is that methadone disrupts adult hippocampal neurogenesis, a form of hippocampal plasticity involved in cognition that is disrupted by other opiates, like morphine. The goal of this study was to determine if methadone alters key parameters of hippocampal neurogenesis in the adult rat. Four groups of male rats were injected with saline (Saline, n=11) or methadone (Escalating, Short Term, Acute, n=10–11/group) over the course of three weeks. Weight gain, locomotor activity, and neurogenesis data were collected. Consistent with prior results, Escalating rats had slower weight gain (−4% vs. Saline). Also consistent with prior results, methadone did not alter locomotor activity over the course of a 90min test. However, closer analysis revealed that methadone – irrespective of the dose or duration – led to a decrease in locomotor activity (−11 to −20% vs. saline) when examined during the first 5min of the locomotor test. Surprisingly, methadone did not alter any of three quantified parameters relevant to adult hippocampal neurogenesis (number of Ki67-, doublecortin-, or BrdU-immunoreactive cells [BrdU given prior to saline/methadone exposure]). These results suggest that – unlike other opiates such as morphine – experimenter-delivered methadone does not alter hippocampal plasticity by decreasing the number of adult-generated neurons.