Cocaine strongly reduces prepulse inhibition in apomorphine-susceptible rats, but not in apomorphine-unsusceptible rats: regulation by dopamine D2 receptors.
Dopaminergic agonists, such as apomorphine and amphetamine, have been shown to drastically reduce prepulse inhibition of the acoustic startle reflex. The effects of the indirect dopamine agonist cocaine on prepulse inhibition have only been described in a few reports and have yielded conflicting results, possibly due to individual differences within and between rat strains. In this study we therefore used apomorphine-susceptible and apomorphine-unsusceptible rats, as an animal model for individual differences, to study the effects of cocaine (20, 30 mg/kg i.p.) on prepulse inhibition. In addition we tested whether the cocaine-induced deficit in prepulse inhibition could be reversed by the D2-antagonist remoxipride (5 mg/kg i.p.), the alpha-1 adrenoceptor antagonist prazosin (2.5 mg/kg i.p.) and the 5-HT2-antagonist ketanserin (2.0 mg/kg i.p.). Cocaine strongly reduced prepulse inhibition in apomorphine-susceptible rats, but had no effect at all on apomorphine-unsusceptible rats. Remoxipride had no effect on prepulse inhibition, but prazosin and ketanserin increased prepulse inhibition. Both remoxipride and prazosin reversed the cocaine-induced deficit in prepulse inhibition, whereas ketanserin did not. We conclude that apomorphine-susceptible rats are extremely sensitive to the effects of cocaine on prepulse inhibition, while apomorphine-unsusceptible rats are not. The effects of cocaine on prepulse inhibition in apomorphine-susceptible rats were mediated by D2-receptors, but not by 5-HT2-receptors or alpha-1 adrenoceptors.
van der Elst
Martine C J
MC
Department of Cognitive Neurosciences, Section Molecular Neurobiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Ellenbroek
Bart A
BA
Cools
Alexander R
AR
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects*; D013045:Species Specificity
D015259:Dopamine Agents; D018377:Neurotransmitter Agents; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D044348:Receptors, Serotonin, 5-HT2; D003042:Cocaine; D001058:Apomorphine