LONG-TERM MONOAMINE DEPLETION, DIFFERENTIAL RECOVERY, AND SUBTLE BEHAVIORAL IMPAIRMENT FOLLOWING METHAMPHETAMINE-INDUCE NEUROTOXICITY

Squads of rats were assayed at three intervals following MA-induced ne urotoxicity to investigate the persistence of monoamine deficits, the potential for monoamine recovery, and spatial task abilities. At 48, 1 39, and 237 days postinjection, MA animals showed significant monoamin e 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 d ays, MPFC and CdN levels were elevated to 70%. Similarly, initial CdN BA reductions (30% nf control levels) showed recovery to 80% by 237 da ys. These findings support neurochemical recovery following MA neuroto xicity. However, the persistent depression of HPC 5-HT suggests that n ot all structures recover equally. The HPC did show elevated turnover (metabolite/neurotransmitter) over time: suggesting a unique compensat ory response. MA treatment also produced an impairment in the Morris w ater-maze place task at 65 days postinjection. No impairments were obs erved in water-maze moving platform or place task at 79 and 165 days p ostinjection, 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. (C) 1998 Elsevier Science Inc.