Motor responses to dopamine D1 and D2 agonists in the reserpine-treated mouse are affected differentially by the NMDA receptor antagonist MK 801

Abstract

The akinesia induced by reserpine in mice was effectively reversed by the dopamine D1 receptor agonists SKF 38393 (5-30 mg/kg IP) and CY 208-243 (1-5 mg/kg IP), and by the mixed D1/D2 agonist pergolide (5 mg/kg SC), but less well by the D2 agonists lisuride, PHNO, LY 171555 and RU 24213 (each at 5 mg/kg SC) and not at all by the NMDA receptor antagonist MK 801 (0.1-10 mg/kg IP). MK 801 potentiated D1-dependent locomotion, but always suppressed rearing and grooming. D2-dependent locomotion was inhibited by MK 801. The D2 agonist RU 24213 was antagonised by as little as 6.25 micrograms/kg MK 801, while PHNO and LY 171555 were antagonised by 0.1 mg/kg MK 801. Lisuride was not inhibited by up to 1.6 mg/kg MK 801. Importantly, all animals showed signs of incapacitation with MK 801 in certain elements of their behaviour, most notably ataxia and hind limb abduction. Thus whilst NMDA receptor blockade can facilitate the restoration of movement by dopamine D1 (though not D2) agonists in monoamine-depleted mice, the fluency of the motor response is adversely affected.

Activation of D1, but not D2 Receptors Potentiates Dizocilpine-Mediated Disruption of Prepulse Inhibition of the Startle

“…Interestingly, the effect of the combination was prevented by pretreatment with the D 1 antagonist SCH 23390, at both given doses, indicating that the observed effect is mediated by D 1 receptors. Taken together, these data provide new and intriguing evidence on the interactions between NMDA and D 1 receptors on sensorimotor gating, and align with other evidence with regard to the ability of D 1 agonists to enhance behavioral effects of NMDA receptor antagonists, such as locomotor activity (Goodwin et al, 1992;Svensson et al, 1992;Martin et al, 1994) and stereotypic responses (Verma and Kulkarni, 1992). Our finding is also consistent with the observation of Dall 'Olio et al (2000) that the administration of dizocilpine prolonged SKF 38393-induced grooming in rats.…”

“…This result induced the authors of the study to discard hypotheses concerning involvement of both receptors in the NMDA receptor antagonistmediated impairment of sensorimotor gating. Nonetheless, manifold reports have underlined the activation of D 1 receptors as having synergistic effects with dizocilpine, in numerous behavioral tests (Goodwin et al, 1992;Verma and Kulkarni, 1992;Dall'Olio et al, 2000). In light of these premises, the present study was designed to elucidate interactions between D 1 and D 2 receptors with dizocilpinemediated disruption of PPI.…”

Interaction between glutamatergic and dopaminergic tone in the nucleus accumbens of mice: evidence for a dual glutamatergic function with respect to psychomotor control

“…Whereas the behavioural stimulation induced by the D-1 agonist SKF 39393 or the mixed D-l/D-2 agonist apomorphine, given in threshold doses, was potentiated by the N-methyl-D-aspartate (NMDA) antagonist MK-801 Carlsson, 1989, 1990), the stimulant actions of D-2 agonists were antagonized by the NMDA antagonist (Svensson et al, 1992). Similar results have been obtained by Morelli and Di Chiara (1990) and by Goodwin et al (1992), using somewhat different experimental models. Thus, the responsiveness of the D-1 receptors is apparently suppressed by the glutamatergic tone.…”

The muscarine antagonist methscopolamine and the NMDA antagonist AP-5 injected unilaterally into the nucleus accumbens cause mice to rotate in opposite directions

“…Moreover, the locomotor stimulation induced by the dopamine D1 agonist SKF 38393 was increased by MK-801, whereas the locomotor stimulation induced by the D2 agonist quinpirole was decreased by MK-801 (Svensson et al, 1992a). Similar results have been obtained by Morelli and Di Chiara (1990) and by Goodwin et al (1992), using somewhat different experimental models. Thus, it seems as if glutamate can both stimulate and inhibit behaviour, and the outcome seems to depend to some extent on whether it interacts with D1 or D2 receptors.…”