Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the exploratory activity of rats in the elevated plus-maze.
Acute administration of gepirone, a 5-HT1A agonist, caused a dose dependent (1-10 mg/kg, IP) reduction in the locomotor activity (open and closed arms) of rats tested in the elevated plus-maze. However, rats housed in individual cages and submitted to chronic treatment with gepirone (10 mg/kg PO) showed a marked increase in the percentages of number and time spent in the open arms as compared to controls. These results are compatible with the idea that the antiaversive effect due to long-term treatment with 5-HT1A agonists is the result of a progressive desensitization of the somatodendritic 5-HT autoreceptor with the consequent recovery of firing rate of 5-HT neurons along with an activation of normosensitive postsynaptic 5-HT neurons. Ketanserin caused a biphasic effects on the exploratory behavior of rats in the plus-maze. The lower dose (0.5 mg/kg) decreased the aversion to the open arms and the higher dose (1.0 mg/kg) caused an unspecific decrease in the overall activity of the animals. Ketanserin is supposed to have antagonistic action on 5-HT2 and on alpha-adrenergic receptors. As prazosin (0.5-1.0 mg/kg), an alpha-adrenergic receptor blocker, did not present any significant effect in the present work it is suggested that the effects of the lower dose of ketanserin was due to its high antagonistic action on 5-HT2 receptors.
Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Brasil.
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Motta
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Maisonnette
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Morato
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Castrechini
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Brandão
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011985:Receptors, Serotonin; D007650:Ketanserin; C039979:gepirone