title: Behavioral, pharmacological and neuroanatomical analysis of serotonin 2C receptor agonism on maternal behavior in rats.
abstract: As a highly motivated social behavior, maternal behavior in rats has been routinely used to study psychoactive drugs for clinical, neuroscience and pharmacological purposes. Recent evidence indicates that acute activation of serotonin 2C (5-HT2C) receptors causes a disruption of rat maternal behavior. The present study was designed to elucidate the behavioral, pharmacological mechanisms and neuroanatomical basis of this 5-HT2Ceffect. First, we replicated the finding that acute MK212 injection (2.0mg/kg, a highly selective 5-HT2Cagonist) disrupts maternal behavior, especially on pup retrieval. Interestingly, this disruption was significantly attenuated by 4-h pup separation (a procedure putatively increased maternal motivation). MK212 also suppressed food retrieval, indicating that it has a general effect on motivated behaviors. Second, we showed that MK212 disrupts maternal behavior by specifically activating 5-HT2Creceptor, as pretreatment with a 5-HT2Creceptor antagonist SB242084 (0.6 and 1.0mg/kg) alleviated MK212-induced disruption on pup retrieval. Third, we microinjected MK212 into various brain regions implicated in the regulation of maternal behavior: nucleus accumbens shell (25, 75, 250ng/0.5μl/side), medial prefrontal cortex (25 and 250ng, 1, 2 and 5μg/0.5μl/side), and medial preoptic area (MPOA, 75ng, 1 and 5μg/0.5μl/side). Pup retrieval and other maternal responses were not affected by any of these manipulations. Finally, we used c-Fos immunohistochemistry to identify the central mechanisms of the acute and repeated MK212 effects on maternal behavior. Acute MK212 (2.0mg/kg) disrupted pup retrieval and concurrently decreased c-Fos expression in the ventral part of lateral septal nucleus (LSv), MPOA, dentate gyrus (DG) and dorsal raphe (DR), but increased it in the central amygdala (CeA). Five days of repeated MK212 (2.0mg/kg) treatment produced a persistent disruption of pup retrieval and only decreased c-Fos expression in the DR. These findings not only confirm a role of 5-HT2Creceptor in rat maternal behavior, but also suggest that the coordinated 5-HT2Cactivity in various limbic (e.g., LSv, DG, CeA), hypothalamic regions (e.g., MPOA) and brainstem areas (e.g. DR), is likely involved in the mediation of important psychological processes (e.g. motor function, motivation) necessary for the normal expression of maternal behavior.
authors: Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA; Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062 Shaanxi, China.
authors: Ruiyong
authors: R
authors: Wu
authors: Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA; Faculty of Psychology, Southwest University, Chongqing, China.
authors: Jun
authors: J
authors: Gao
authors: Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
authors: Shinnyi
authors: S
authors: Chou
authors: Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
authors: Collin
authors: C
authors: Davis
authors: Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA. Electronic address: mli@unl.edu.
authors: Ming
authors: M
authors: Li
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D005260:Female; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects*; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; C014896:6-chloro-2-(1-piperazinyl)pyrazine
keywords: MK212; Maternal behavior; Maternal motivation; Pup retrieval; SB242084; Serotonin 2C receptor