Long-term monoamine depletion, differential recovery, and subtle behavioral impairment following methamphetamine-induced neurotoxicity.

Squads of rats were assayed at three intervals following MA-induced neurotoxicity to investigate the persistence of monoamine deficits, the potential for monoamine recovery, and spatial task abilities. At 48, 139, and 237 days postinjection, MA animals showed significant monoamine depletions compared with controls. Investigating percent depletions (MA/control) across time showed monoamine recovery in some structures. Initially, 5-HT within medial prefrontal cortex (MPFC), caudate (CdN), and hippocampus (HPC) was reduced to 30% of control levels. By 237 days, MPFC and CdN levels were elevated to 70%. Similarly, initial CdN DA reductions (30% of control levels) showed recovery to 80% by 237 days. These findings support neurochemical recovery following MA neurotoxicity. However, the persistent depression of HPC 5-HT suggests that not all structures recover equally. The HPC did show elevated turnover (metabolite/neurotransmitter) over time, suggesting a unique compensatory response. MA treatment also produced an impairment in the Morris water-maze place task at 65 days postinjection. No impairments were observed in water-maze moving platform or place task at 79 and 165 days postinjection, respectively, or in T-maze alternation. The possibility that partial recovery in tissue monamine levels underlies the sparing of function and behavioral improvement is discussed.