Envolvimento de receptores 5-HT2C do hipocampo ventral em comportamentos de defesa de ratos no labirinto em cruz elevado / Involvement of ventral hippocampus 5-HT2C receptors on defensive behaviors of rats in the elevated plus-maze

A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV) previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE). Quinze minutos após injeções intraperitoniais (IP, 1ml/kg) do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg). Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.

Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH) prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM). Fifteen minutes after intraperitonial (IP, 1ml/kg) injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg), rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg) into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections. These results not only further confirm the anxiogenic-like action of 5-HT2C agonists, but also suggest that this behavioral profile might be mediated at least in part by VH 5-HT2C receptors.

Effects of two selective 5-HT2C receptor-acting compounds into the ventral hippocampus of rats exposed to the elevated plus-maze

This study investigated the effects of two selective serotonin2C (5-hydroxytryptamine, 5-HT2C) receptor-acting compounds into the ventral hippocampus (VH) of rats exposed to the elevated plus-maze (EPM). In the first experiment, rats were exposed to the EPM 10 min following VH infusions of either vehicle or the selective 5-HT2C-receptor agonist RO-60-0175 (0.3, 1.0, 3.0 and 10.0µg). In addition to conventional parameters of open arm exploration (i.e. percentages of open arm entries and of time spent in these arms), risk assessmentrelated behaviors were recorded as anxiety-like measures in EPM scoring. RO-60-0175 selectively decreased open arm exploration at the dose of 1.0 µg, while inducing locomotor-suppressant effects at the two highest doses. In the second experiment, VH infusions of the selective 5-HT2C antagonist RS 102221 (0.75, 1.25 and 2.5 µg) did not affect open arm exploration, while reducing risk assessment in the closed ones. This behavioral profile of risk assessment is suggestive of an anxiolytic-like action. These results further corroborate our previous findings showing that VH 5-HT2C receptor activation elicits anxiogenic-like and locomotor-suppressant effects, and suggest that the selective blockade of this receptor is accompanied by an anxiolytic-like action as detected by ethologically derived measures in the EPM.