title: Implication of the 5-HT2A and 5-HT2C (but not 5HT1A) receptors located within the periaqueductal gray in the elevated plus-maze test-retest paradigm in mice.
abstract: A single exposure to the elevated plus-maze test (EPM) increases open arms avoidance and reduces or abolishes the anxiolytic-like effect of benzodiazepines assessed during a second trial, a phenomenon defined as "one-trial tolerance" (OTT). It has been emphasized that the dorsal portion of the midbrain periaqueductal gray (dPAG) plays a role on this enhanced aversion phenomenon in maze-experienced rodents. Given that intra-dPAG injections of a wide range of serotonergic 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptor agonists produce anxiolytic-like effects in maze-naïve rodents, the present study examined the effects of the 5-HT(1A) receptor agonist 8-OH-DPAT (5.6 and 10.0nmol in 0.15microl) the preferential 5-HT(2A) receptor agonist DOI (2.0 and 8.0nmol in 0.1microl) and the preferential 5-HT(2C) receptor agonist MK-212 (21.2 and 63.6nmol in 0.1microl) microinjected into the dPAG prior to Trial 1 and Trial 2 on the behaviour of mice in the EPM. Test sessions were recorded and subsequently scored for anxiety-like behaviour (percentage of open arms entries and time) as well as general locomotor activity (closed arm entries). The results showed a lack of 8-OH-DPAT (5.6 and 10.0nmol) effect on the behaviour of maze-naïve and maze-experienced mice, while intra-dPAG microinfusions of DOI (8nmol) reduced anxiety-like behaviour only in maze-experienced mice that had received a similar treatment prior to Trial 1. Furthermore, intra-dPAG MK-212 (63.6nmol) showed an anxiolytic-like effect on both Trial 1 and Trial 2. Importantly, these effects were observed in the absence of any significant change in closed arm entries, the parameter considered to be a valid index of locomotor activity in the plus-maze. These results support the dPAG as a crucial structure involved in the neurobiology of the OTT phenomenon as well as accounting the role of the 5-HT(2A) and 5-HT(2C) receptors located within this midbrain structure on the emotional state induced by EPM test and retest paradigm mice.
authors.affiliation: Programa de Pós-Graduação em Psicobiologia, FFCLRP-Campus USP, Ribeirão Preto, SP 14040-901, Brazil.
authors.forename: K S
authors.initials: KS
authors.lastname: Gomes
authors.forename: R L
authors.initials: RL
authors.lastname: Nunes-De-Souza
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000473:pathology* / Q000503:physiopathology; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008845:Microinjections / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D015203:Reproducibility of Results; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D018490:Serotonin Agents / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D011719:Pyrazines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D018490:Serotonin Agents; D044282:Receptor, Serotonin, 5-HT1A; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine