Behavioural topography in the striatum: differential effects of quinpirole and d-amphetamine microinjections
Introduction
A large body of evidence suggests that the striatum is organised as a mosaic of neurochemical compartments that maintain specific relationships with its afferent and efferent systems (Graybiel, 1990; Groenewegen et al., 1991; Gerfen, 1992). The entire cortical mantle provides topographically organized projections to the striatum (DeLong and Georgopoulos, 1981; McGeorge and Faull, 1989; Parent and Hazrati, 1995). These anatomical findings encouraged the view that the striatum is functionally heterogenous. More recent anatomical studies provided further support for this notion by suggesting that cortical information is segregated at the anatomical and functional levels through multiple basal ganglia-thalamo-cortical circuits, of which the striatum is an intrinsic part (Alexander and Crutcher, 1990; Groenewegen et al., 1990; Hoover and Strick, 1993). The striatum is the major target not only for cortical, but also for limbic inputs, and its complex mosaic-like ordering of afferent/efferent connections and neurochemical compartments provides the basis for parallel processing of motor, associative and cognitive functions.
The evidence provided by anatomical and neurochemical studies was reinforced by the finding that specific subterritories of the striatum made selective contributions to behavioural processes (Iversen, 1984; Pisa, 1988; Robbins and Everitt, 1992). In this context, focal lesion and microinjection studies indicated that different sectors of the striatum are selectively involved in complex forms of behaviour. For example, in the rat, selective excitotoxic lesions of the ventrolateral striatum resulted in selective impairments in feeding behaviours and skilled motor performance, as observed in reaching and food-manipulation tasks (Dunnett and Iversen, 1982a, Dunnett and Iversen, 1982b; Pisa, 1988; Pisa and Cyr, 1990). By contrast, lesions of the nucleus accumbens specifically affected the appetitive aspects of motivated behaviour, including food hoarding induced by deprivation and approach to primary reinforcers (Iversen, 1984; Robbins and Everitt, 1992). The use of the intracerebral microinjection technique added convincing evidence supporting heterogeneity of function in the striatum in terms of responsiveness to drugs acting as direct or indirect dopamine agonists. In this regard, it became well-documented that the nucleus accumbens was crucially implicated in the psychomotor-activating and the reinforcing effects of dopamine and of the psychostimulants amphetamine and cocaine (Costall and Naylor, 1975; Taylor and Robbins, 1984; Jones et al., 1981; Hooks et al., 1993). In turn, the ventrolateral striatum was linked to the induction of stereotyped oral behaviours, including biting and directed movements of the paw to the mouth, which were observed readily after intracerebral microinjections of amphetamine into this sector (Kelley et al., 1988; Delfs and Kelley, 1990; Dickson et al., 1994).
While studies on the behavioural effects of intrastriatal administration of indirectly acting dopamine receptor agonists, such as amphetamine and cocaine, clearly show functional differences across subterritories in the striatum, the contribution of the different classes of dopamine receptors within these striatal sectors to the expression of behaviour has been less studied. Drugs which result in release of endogenous dopamine activate all classes of dopamine receptors. There are, however, dopamine agonists with greater degrees of selectivity for particular classes of dopamine receptors. In the present experiments, we compare the behavioural effects of microinjections of amphetamine with those elicited by the D2-class dopamine receptor agonist quinpirole following administration into three anatomically distinct sites in the striatum: the nucleus accumbens, the ventrolateral striatum and the anterodorsal striatum.
Section snippets
Animals and surgery
Wistar rats (n=30), weighing 200–275 g at arrival in the laboratory, were used for these experiments, allowed to acclimatise to the laboratories for at least three days, and handled extensively for another four days before surgery. They were initially housed in pairs under constant conditions of temperature (19.0–21.0°C), relative humidity (60–65%) and light–dark cycle (12:12 h, lights on at 8:00 a.m.), with standard laboratory rat chow and tap water available ad libitum. Rats weighed 250–325 g
Results
The ANOVA indicated significant effects of quinpirole [F(1,27)=29.262, p<0.0001] and of amphetamine [F(1,27)=59.557, p<0.0001] on rearing behaviour. Quinpirole produced a significant reduction in rearing behaviour when administered into the nucleus accumbens (t=3.27, p<0.01), or into the ventrolateral striatum (t=4.05, p<0.01) (Fig. 2). A nonsignificant trend was observed in animals treated with quinpirole into the anterodorsal striatum (t=2.06, p<0.10). In turn, amphetamine microinjections
Discussion
The results of the present study include several findings related to the effects of the D2-class receptor agonist quinpirole and the indirect agonist amphetamine on unconditioned motor behaviours following direct administration into the striatum.
Conclusions
Quinpirole microinjections revealed that a considerable degree of functional overlap exists across striatal territories for the expression of certain motor behaviours. This D2-class dopamine receptor-mediated substrate is linked to processes leading to behavioural inactivation, together with the emergence of sedation, yawning and oral dyskinesias. Thus, the striatum is not topographically organised for the mediation of D2-class dopamine receptor-induced sedation, yawning and motor inhibition.
Acknowledgements
The present work was funded by the Wellcome Trust, and the Medical Research Council of the UK. J.J.C. was in receipt of a Medical Research Council scholarship. The authors also express their gratitude to Gregory Daubney and Henry Hall for technical assistance.
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