Enhanced dopamine metabolism in accumbens leads to motor activity and concurrently to increased output from nondopamine neurons in ventral tegmental area and substantia nigra

Abstract

We previously have reported that nondopamine (non-DA) neurons in substantia nigra (SN) and ventral tegmental area (VTA) of the rat show increased discharge rates during amphetamine (AMPH) and apomorphine (APO)-induced motor activity. The present study represents an attempt to determine the contribution of nucleus accumbens (ACC) dopaminergic activity to these effects, and to ascertain whether the effects in VTA differ from those seen in SN when dopaminergic activity is enhanced locally in ACC. The experiments were carried out in male albino rats (300-400 g) chronically implanted with multiple fine wire electrodes (62 microns) aimed at the pars reticulata of SN (SNR) and VTA. Unit activity was recorded extracellularly in the behaving rat, from neurons identified on the basis of the properties of their action potentials as representing the output of the non-DA neurons in these two structures. In each drug session, unit activity was recorded in parallel from several probes, while motor activity was measured with the open-ended wire technique. But with the recording technique used, a unit represented in most instances the output of a small family of neurons (3-10). Each animal underwent a series of tests given on consecutive days. During these tests, motor and unit activity were measured for 90 min before the drug was administered, and for 135 min after. The first test was of the effects of AMPH, 5 mg/kg, given by the systemic route. The second was of the effects of saline containing 0.1% ascorbic acid (the vehicle) injected bilaterally in ACC, in a volume of 2 microliters per side. The third and all subsequent tests were of the effects of a mixture containing 40 micrograms AMPH, 20 micrograms DA, and 20 micrograms pargyline (P) dissolved in 2 microliters of the vehicle, injected bilaterally in ACC. The results showed that systemic AMPH made the animal hyperactive and at the same time, increased the discharge rate of the non-DA neurons. The bilateral injections of the vehicle in ACC, increased motor activity for about 7 min, an effect interpreted as a rebound from the restraint of the animal during the intracerebral injections, and then depressed motor throughout the 135 min of the postinjection recording period. The effect of the vehicle was to depress unit activity. The effects of injecting the mixture in ACC was to increase motor activity, but with the magnitude and duration of the increase depending on the number of treatments received.(ABSTRACT TRUNCATED AT 400 WORDS)