title: Nicotinic antagonist effects in the mediodorsal thalamic nucleus: regional heterogeneity of nicotinic receptor involvement in cognitive function.
abstract: Nicotine has been found in many studies to improve cognitive function. However, some studies have not found this effect and others have seen nicotine-induced impairments. Systemic administration bathes the brain with drugs. However, the brain is quite intricately organized with various regions playing very different roles in the bases of cognitive function. We have examined the role of nicotinic receptors in a variety of brain areas for memory. In the hippocampus and amygdala, local infusions of both alpha7 and alpha4beta2 antagonists methyllyaconitine (MLA) and dihydro-beta-erythroidine (DHbetaE) significantly impair memory. In the current studies we locally infused acute and chronic doses of MLA and DHbetaE into the mediodorsal thalamic nucleus and tested memory function on a 16-arm radial maze. The rats also received systemic nicotine to determine the impact of more generalized nicotine effects. Since nicotinic treatments are being developed for cognitive impairment of schizophrenia, interactions were studied with the antipsychotic drug clozapine. In the acute study, the 6.75 microg/side of DHbetaE improved working memory. Co-administration of MLA reversed the DHbetaE-induced improvement. Chronic DHbetaE infusions into the mediodorsal thalamic nucleus also improved working memory. Systemic nicotine reversed this effect. Clozapine had no significant interaction. Nicotinic alpha4beta2 receptors in the mediodorsal thalamic nucleus appear to play an opposite role with regard to working memory than those in the hippocampus and amygdala. Heterogeneity in response to nicotinic drugs given systemically may be due to anatomically distinct nicotinic systems in the brain and their unique roles in the neural bases of cognitive function.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Reginald
authors.initials: R
authors.lastname: Cannady
authors.forename: Ruth
authors.initials: R
authors.lastname: Weir
authors.forename: Boyoung
authors.initials: B
authors.lastname: Wee
authors.forename: Emily
authors.initials: E
authors.lastname: Gotschlich
authors.forename: Nadeem
authors.initials: N
authors.lastname: Kolia
authors.forename: Edward
authors.initials: E
authors.lastname: Lau
authors.forename: Jesse
authors.initials: J
authors.lastname: Brotherton
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003071:Cognition / Q000502:physiology*; D004079:Dihydro-beta-Erythroidine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D018782:Maze Learning / Q000187:drug effects; D020645:Mediodorsal Thalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D014150:Antipsychotic Agents; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D003024:Clozapine; D000157:Aconitine