title: DOI-induced deficits in prepulse inhibition in Wistar rats are reversed by mGlu2/3 receptor stimulation.
abstract: Prepulse inhibition (PPI) of the acoustic startle response (ASR) provides a measure of sensorimotor gating mechanisms that are impaired in schizophrenia patients. Interactions of the serotonin (5-hydroxytryptamine, 5-HT) and glutamatergic systems, especially via the 5-HT(2A) receptor subtype, have been implicated in the regulation of PPI. The present study investigated the involvement of interactions between 5-HT(2A) and metabotropic glutamate (mGlu)2/3 receptors in modulating PPI in Wistar and Lister Hooded rats. Systemic administration of the 5-HT(2A/2C) receptor agonist DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride; 3mg/kg) reduced PPI and ASR magnitude in Wistar but not in Lister Hooded rats. In Wistar rats, pre-treatment with the mGlu2/3 receptor agonist LY379268 (1mg/kg) attenuated the DOI-induced disruption of PPI as well as the DOI-elicited reductions of ASR magnitude. LY379268 itself did not alter PPI in both strains and only slightly increased ASR magnitudes in Wistar rats. Taken together, these findings support the notion of functionally antagonistic interactions between 5-HT(2A) and mGlu2/3 which might be involved in regulating sensorimotor gating mechanisms. Additionally, the data suggest that stimulation of mGlu2/3 receptors may be useful to ameliorate sensorimotor gating deficits resulting from an overstimulation of 5-HT(2A) receptors.
authors.affiliation: University of Bremen, Brain Research Institute, Department of Neuropharmacology, COGNIUM, 28359 Bremen, Germany. lena_wischhof@yahoo.de
authors.forename: Lena
authors.initials: L
authors.lastname: Wischhof
authors.forename: Helena E A
authors.initials: HE
authors.lastname: Aho
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000596:Amino Acids / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D007266:Inhibition, Psychological; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000596:Amino Acids; D000662:Amphetamines; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; D017366:Serotonin Receptor Agonists; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine