title: Startle gating in rats is disrupted by chemical inactivation but not D2 stimulation of the dorsomedial thalamus.
abstract: The neural regulation of sensorimotor gating, as measured by prepulse inhibition (PPI) of the startle reflex, has been a focus of interest based on the consistent deficits in PPI reported in schizophrenia patients. While dorsomedial thalamus (MD) dysfunction has been implicated in the clinical 'gating' deficits of schizophrenia patients, relatively little is known regarding the regulation of PPI by the MD. We previously reported that PPI in rats is reduced after intra-MD infusion of the GABA agonist muscimol, or after excitotoxic lesions of the MD. In the present study, we tested the regulation of PPI by D2 receptors in the MD. PPI was measured after intra-MD infusion of the D2 agonist quinpirole (0, 1 or 10 microg/side) in a within-subject design. Infusion placement was confirmed functionally in later tests by reversible inactivation of the MD via intra-MD infusion of tetrodotoxin (TTX; 10 ng/side), and subsequently by direct histological examination. Intra-MD infusion of quinpirole had no significant effect on PPI, using doses that significantly disrupt PPI after infusion into the ventral forebrain (nucleus accumbens). TTX infusion into the MD caused a significant loss of PPI; this effect was not reversed by pretreatment with the atypical antipsychotic quetiapine (7.5 mg/kg). The MD regulation of PPI in rats is not mediated via D2 receptors, but is clearly manifested via PPI deficits after reversible MD inactivation via TTX.
authors.affiliation: Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA. nswerdlow@ucsd.edu
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.forename: Leia
authors.initials: L
authors.lastname: Pitcher
authors.forename: Hea Ran
authors.initials: HR
authors.lastname: Noh
authors.forename: Jody M
authors.initials: JM
authors.lastname: Shoemaker
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003987:Dibenzothiazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000166:cytology / Q000502:physiology*; D000069348:Quetiapine Fumarate; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D026941:Sodium Channel Blockers; D019257:Quinpirole; D000069348:Quetiapine Fumarate; D013779:Tetrodotoxin; D004298:Dopamine