1. ¹'Guy Everett' Laboratory, Department of Neuroscience, Center of Excellence 'Neurobiology of Dependence', Monserrato (CA), Italy
2. ²Department of Experimental Biology, University of Cagliari, Monserrato (CA), Italy
3. ³Department of Psychology, Ohio State University, Columbus, OH, USA

Correspondence: Dr M Bortolato, Dipartimento di Neuroscienze 'Bernard B. Brodie', University of Cagliari, Cittadella Universitaria S.S. 554 Km 4,500, 09042 Monserrato (CA), Italy. Tel: +39 070 6754342; Fax: +39 070 6754320; E-mail: marco.bortolato@inwind.it

Received 25 March 2004; Revised 20 July 2004; Accepted 22 July 2004; Published online 25 August 2004.

Abstract

Although substantial evidence has shown interactions between glutamatergic and dopaminergic systems play a cardinal role in the regulation of attentional processes, their involvement in informational filtering has been poorly investigated. Chiefly, little research has focused on functional correlations between the dopaminergic system and the mechanism of action of N-methyl-D-aspartate (NMDA) receptor antagonists on sensorimotor gating. The present study was targeted at evaluating whether the activation of D₁ and D₂ receptors is able to interact with the disruption of prepulse inhibition (PPI) of startle mediated by dizocilpine, a selective, noncompetitive NMDA receptor antagonist. We tested the effects of SKF 38393 (()-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol) (10 mg/kg, s.c.), a selective D₁ agonist, and quinpirole (0.3, 0.6 mg/kg, s.c.), a D₂ agonist, in rats, per se and in cotreatment with different doses of dizocilpine, ranging from 0.0015 to 0.15 mg/kg (s.c.). Subsequently, the effect of the D₁ antagonist SCH 23390 ((R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) (0.05, 0.1 mg/kg, s.c.) on PPI disruptions mediated by dizocilpine and by combination of dizocilpine and SKF 38393 was tested. Two further experiments were performed to verify whether the synergic effect of the D₁ agonist with dizocilpine was counteracted by effective doses of haloperidol (0.1, 0.5 mg/kg, i.p.) and clozapine (5, 10 mg/kg, i.p.). All experiments were carried out using standard procedures for the assessment of PPI of the acoustic startle reflex. SKF 38393, while unable to impair sensorimotor gating alone, induced PPI disruption in cotreatment with 0.05 and 0.15 mg/kg of dizocilpine, both ineffective per se. Furthermore, this effect was reversed by SCH 23390, but not by haloperidol or clozapine. Conversely, no synergistic effect was exhibited between quinpirole and dizocilpine, at any given dose. These findings suggest that D₁, but not D₂ receptors, enhance the disruptive effect of dizocilpine on PPI.