Behavioral effects of xylamine-induced depletions of brain norepinephrine: interaction with amphetamine

Male rats were treated with a combination of systemic fluoxetine and intraventricular xylamine in order to deplete brain norepinephrine (NE) in the projection areas of the locus coeruleus. Liquid chromatographic measures confirmed that xylamine reduced hippocampal NE by 77%. Four days later, control and lesioned rats were tested following subcutaneous injections of either saline or 1.0 mg/kg amphetamine in a Behavioral Pattern Monitor which recorded the sequential patterns of their locomotor and investigatory (holepokes) responses. Relative to controls, NE-depleted rats exhibited no alteration in the amount of spontaneous locomotor activity or its rate of habituation, but made fewer rearings and holepokes, particularly early in the hour test session. When challenged with 1.0 mg/kg amphetamine, sham-lesioned rats exhibited the expected increases in locomotor activity, holepokes, rearings, and both entries into and time spent in the center of the chamber. The lesioned animals exhibited a potentiation of the amphetamine effect on center activity and a diminished effect of amphetamine on holepoking and rearings. Control and lesioned rats were again tested at 18 days postlesion using the same test paradigm. The previously noted effects of the lesions on spontaneous behavior were absent at 18 days. Furthermore, the ability of these NE depletions to alter the behavioral effects of 1.0 mg/kg amphetamine at 4 days postlesion largely disappeared by 18 days. These results are indicative of some compensatory mechanism(s) operating to restore normal function between 4 and 18 days after the introduction of the lesion.