title: Control of hippocampal theta rhythm by serotonin: role of 5-HT2c receptors.
abstract: The hippocampus plays an important role in learning and memory and has been implicated in a number of diseases, including epilepsy, anxiety and schizophrenia. A prominent feature of the hippocampal network is the capability to generate rhythmic oscillations. Serotonergic modulation is known to play an important role in the regulation of theta rhythm. 5-HT2c receptors represent a specific target of psychopharmacology and, in particular, the behavioral effects of the 5-HT2c receptor agonist mCPP have been thoroughly tested. The present study used this compound and the selective 5-HT2c receptor antagonist SB-242084 to elucidate the role of 5-HT2c receptors in the generation of hippocampal oscillations. Hippocampal EEG was recorded and the power in the theta frequency range was monitored in different behaviors in freely-moving rats and after brainstem stimulation in anesthetized animals. We found that in freely-moving rats, mCPP suppressed hippocampal theta rhythm and the effect was stronger during REM sleep than during waking theta states. Under urethane anesthesia, mCPP decreased the power for both spontaneous and elicited theta rhythm in a dose-dependent manner and the 5-HT2c antagonist reversed this effect. The results of this study demonstrate that 5-HT2c receptors are important element of the serotonergic modulation of hippocampal theta oscillations and thus pharmacological interactions with these receptors can modulate physiological and pathological processes associated with limbic theta activity.
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Elin
authors.initials: E
authors.lastname: Sörman
authors.forename: Dannie
authors.initials: D
authors.lastname: Wang
authors.forename: Mihaly
authors.initials: M
authors.lastname: Hajos
authors.forename: Bernat
authors.initials: B
authors.lastname: Kocsis
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001933:Brain Stem; D046690:Deep Brain Stimulation; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D012895:Sleep, REM; D013826:Theta Rhythm / Q000187:drug effects; D013997:Time Factors
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine