TIME-DEPENDENT EFFECTS OF REPEATED AMPHETAMINE TREATMENT ON NOREPINEPHRINE IN THE HYPOTHALAMUS AND HIPPOCAMPUS ASSESSED WITH IN-VIVO MICRODIALYSIS

The effects of repeated amphetamine (AMPH) pretreatment on norepinephr ine (NE) neurotransmission in the hypothalamus and hippocampus were as sessed using in vivo microdialysis. Rats were pretreated with either s aline or an escalating-dose AMPH regimen (1-->10 mg/kg) over 10 consec utive days, and then were withdrawn from AMPH for either 1 day or 30 d ays, at which time the animals underwent two consecutive days of testi ng. As expected, repeated treatment with AMPH resulted in time-depende nt changes in both spontaneous locomotor activity and in the psychomot or response to a subsequent challenge injection of AMPH. In addition, repeated exposure to AMPH resulted in time-dependent and regionally-sp ecific changes in the basal concentrations of NE in dialysate, and in the NE response to an AMPH challenge. For example, AMPH pretreatment p roduced a persistent (at least one month) increase in the basal concen tration of NE in the hippocampus, but not the hypothalamus, although t he response to an AMPH challenge was altered in both structures. If is suggested that AMPH treatment produces adaptations in NE systems that far outlast the acute effects of the drug, and that these may contrib ute to both transient and more persistent behavioral sequelae associat ed with the discontinuation of chronic AMPH use. (C) 1997 American Col lege of Neuropsychopharmacology. Published by Elsevier Science Inc.