Enhancement of the acoustic startle response in rats by the dopamine D1 receptor agonist SKF 82958.

Abstract

The present series of experiments was conducted in order to assess the nature of dopaminergic modulation of the acoustic startle response using agonists and antagonists specific for dopamine D1 and D2 receptors. The objective of the present study was to demonstrate an enhancement of the acoustic startle response by dopamine D1 receptor agonists and to characterize this effect pharmacologically in terms of dose-response and selective antagonism at both the dopamine D1 and D2 receptor using a varied range of startle-eliciting intensities. Male Sprague-Dawley rats were injected subcutaneously with the dopamine D1 receptor agonist SKF 82958 (0, 0.01, 0.1, 1, or 3 mg/kg) or SKF 81297 (3 mg/kg) and their startle response was measured across a range of startle-eliciting intensities. For testing with the dopamine D1 or D2 receptor antagonists, animals received injections of either SCH 23390 (0.01 and 0.1 mg/kg) or raclopride (0.1 and 1 mg/kg) 10 min before the challenge with SKF 82958 (1 mg/kg). Systemic administration of SKF 82958 produced a marked enhancement of startle over a wide range of startle intensities. This effect was dose-dependent, with a dose of 1 mg/kg producing the maximal amount of startle enhancement at each intensity. SKF 81297 (3 mg/kg) also produced a robust enhancement of startle. Pretreatment with SCH 23390 produced a dose-dependent blockade of the enhancement of startle by SKF 82958. Pretreatment with raclopride blocked the enhancement of startle by SKF 82958 at the low intensities and attenuated the enhancement at the high intensities. These data suggest that dopamine D1 receptor agonists enhance the acoustic startle response. Furthermore, this effect is dependent on a cooperative type of D1/D2 receptor interaction whereby D2 receptor activation is necessary for the full expression of the D1 receptor-mediated enhancement of startle.