title: Rat strain differences in the ability to disrupt sensorimotor gating are limited to the dopaminergic system, specific to prepulse inhibition, and unrelated to changes in startle amplitude or nucleus accumbens dopamine receptor sensitivity.
abstract: Previous studies indicate that a variety of pharmacological agents interfere with the prepulse inhibition of the acoustic startle (PPI) response including phencyclidine (PCP), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), amphetamine, and apomorphine. Strain differences have been observed in the ability of apomorphine to disrupt PPI, although the degree to which these strain differences occur after administration of nondopaminergic drugs or the degree to which differences can be observed in other models of dopamine (DA) receptor activation has not been elucidated. The present study tested the effects of apomorphine, amphetamine, 8-OH-DPAT, and PCP on PPI in the Sprague Dawley and Wistar rat strains. Because apomorphine disrupts PPI via activation of DA receptors in the nucleus accumbens, apomorphine-induced hyperlocomotion, also a behavioral model of nucleus accumbens DA receptor activation, was measured in both rat strains. Administration of PCP or 8-OH-DPAT attenuated PPI in both strains, whereas apomorphine and amphetamine only attenuated PPI in Wistar rats. The ability of apomorphine to increase motor activity in the absence of a startle-eliciting stimulus was similar in the two strains, as was apomorphine-induced hyperlocomotion. A time course analysis of the effects of apomorphine on startle response in Sprague Dawley rats found that changes in the magnitude of PPI followed changes in basic startle amplitude. Similarly, no apomorphine-induced attenuation of PPI was observed in Sprague Dawley rats after 6-OHDA-induced DA receptor supersensitivity in the nucleus accumbens. These data suggest a dissociation between the effects of DA receptor agonists in PPI and other behavioral models of DA receptor activation.
authors.affiliation: Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, CM 20 2QR United Kingdom.
authors.forename: G G
authors.initials: GG
authors.lastname: Kinney
authors.forename: L O
authors.initials: LO
authors.lastname: Wilkinson
authors.forename: K L
authors.initials: KL
authors.lastname: Saywell
authors.forename: M D
authors.initials: MD
authors.lastname: Tricklebank
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000161:Acoustic Stimulation; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors
chemical_list: D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine; D000661:Amphetamine; D010622:Phencyclidine; D001058:Apomorphine; D004298:Dopamine