Repeated Methamphetamine Administration Results in Axon Loss Prior to Somatic Loss of Substantia Nigra Pars Compacta and Locus Coeruleus Neurons in Male but Not Female Mice

Methamphetamine (meth) is a neurotoxic psychostimulant that increases monoamine oxidase (MAO)-dependent mitochondrial oxidant stress in axonal but not somatic compartments of substantia nigra pars compacta (SNc) and locus coeruleus (LC) neurons. Chronic meth administration results the degeneration SNc LC neurons male mice, MAO inhibition neuroprotective, suggesting deleterious effects chronic begin axons before advancing to soma To test this hypothesis, mice were administered (5 mg/kg) for 14, 21, or 28 days, lengths numbers quantified. In axon decreased with days meth, whereas loss was only observed after meth; (phenelzine; 20 prevented contrast, (28-day) had no effect on length female mice. The demonstrate repeated exposure produces deficits prior subjects, consistent dying-back pattern degeneration, are resistant meth-induced degeneration.