Amphetamine-induced increase in motor activity is correlated with higher firing rates of non-dopamine neurons in substantia nigra and ventral tegmental area.
The responses of non-dopamine neurons in substantia nigra and ventral tegmental area to systemic amphetamine were investigated in the behaving rat chronically implanted with multiple fine-wire electrodes. The neurons were identified with electrophysiological criteria requiring that the signals be of biphasic shape, short duration (less than 2.0 ms), and show high and regular rates of discharge (greater than 20 spikes/s). In recording sessions lasting 240 min, single and multiple unit activity was recorded from seven electrodes, and motor activity was measured automatically with the open-ended wire technique. The movement counts provided an index of gross motor activity, not of the specific movements occurring during DA behaviors. D-Amphetamine, 5.0 mg/kg, given by the intraperitoneal route at 90 min into the session, induced an increase in motor activity and in the firing rate of some non-dopamine neurons. The behavioral and neural responses were correlated for magnitude, latencies and duration. But not all non-dopamine neurons in ventral tegmental area, and substantia nigra showed responses to amphetamine. When unit responses were obtained, they were obtained in subjects which showed large motor responses. In substantia nigra, responsive and non-responsive units were interdigitated and found mainly in the pars reticulata subdivision. In the ventral tegmental area, responsive and non-responsive neurons were interdigitated throughout this structure. The effects of amphetamine were dose-responsive, doses of 1.0, 2.0 and 3.0 mg/kg inducing smaller behavioral and unit responses than 5.0 mg/kg. D-Amphetamine, 5.0 mg/kg, was more effective than L-amphetamine, given at the same dose, in inducing these changes. In rats pretreated with systemic haloperidol, 1.5 mg/kg, the behavioral and neural responses to D-amphetamine, 5.0 mg/kg, were greatly attenuated. In rats pretreated with a subanesthetic dose of urethan, 600 mg/kg, to prevent changes in gross motor activity, the response to D-amphetamine in ventral tegmental area was attenuated, but it was of normal magnitude in substantia nigra. In rats with bilateral electrolytic lesions of nucleus accumbens, D-amphetamine induced a smaller motor response than in controls, but the neural responses in ventral tegmental area and substantia nigra were the same as in controls. These findings support the notion that non-dopamine neurons in ventral tegmental area and substantia nigra, pars reticulata, play a role in the motor function of the A9 and A10 dopamine neurons, and in the behavioral effects of amphetamine.(ABSTRACT TRUNCATED AT 400 WORDS)
Olds
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Division of Biology, California Institute of Technology, Pasadena 91125.
D000200:Action Potentials / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*; D014520:Urethane / Q000494:pharmacology
D014520:Urethane; D006220:Haloperidol; D003913:Dextroamphetamine