The response of non-dopamine neurons in substantia nigra and ventral tegmental area to amphetamine and apomorphine during hypermotility: the striatal influence

Abstract

The effects of haloperidol pretreatment in striatum on the motor response, and on concurrently recorded unit responses of non-dopamine (DA) neurons in substantia nigra (SN) and ventral tegmental area (VTA) to systemic amphetamine and apomorphine, were investigated with the objective of determining the role of the striatum in the output of putative DA output neurons. Unit and motor activity were recorded in the male rat, chronically implanted with 9 electrodes in SN and VTA and with two cannulae for bilateral injections into striatum. The recording electrodes were 3 bundles of 3 wires, each wire in the bundle of a different length, but all 3 aimed at SN, pars reticulata, or VTA. In each recording session, unit activity was derived from 7 wires while gross motor activity was recorded with the open-ended wire technique. The subjects were tested under two conditions. In the first, the vehicle was injected bilaterally into striatum 90 min before one of the DA agonists was injected by the intraperitoneal route. In the second, the DA antagonist haloperidol was injected bilaterally into striatum before the systemic treatment with the DA agonist. In subjects which received injections of the vehicle into striatum, amphetamine induced a large motor response, and concurrently, a large increase in the rate of discharge of a portion of the identified non-DA neurons in SN and VTA. In subjects which received injections of haloperidol into striatum, amphetamine induced a smaller behavioral response, and a smaller increase in the rate of discharge of these neurons in SN but not in VTA where the increase was of the same magnitude as in controls. In control subjects, apomorphine induced an increase in motor activity and concurrently, an increase in the rate of firing of the identified non-DA neurons in SN and VTA. But the increases were of somewhat smaller magnitude and much shorter duration than the increases induced by amphetamine. In subjects which had been pretreated with haloperidol in striatum, apomorphine induced an increase in motor activity that was of the same magnitude as the increase induced in control animals, but the increase in rate of firing in both VTA and SN was reduced. These results lead to the conclusion that the striatum has the capacity to influence the output of non-DA neurons not only in SN but also in VTA, indicating that, if there is a specialization of function, it is only relative. The type of influence exerted appeared to depend on the nature of the motor activity expressed, that is on the type of movement induced by the DA agonists in a situation where a large portion of DA receptors in a prime terminal field was not available for activation because of the pretreatment with haloperidol. It thus appears that the anatomical and partial functional continuum existing at the level of the DA neurons in SN and VTA, may well extend to the non-DA efferent neurons of these two structures.