Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats

Author(s)

Sant'Ana, Ana Beatriz ^[1] ; Vilela-Costa, Heloisa Helena ^[1] ; Vicente, Maria Adrielle ^[1] ; Hernandes, Paloma Molina ^[1] ; Carneiro Spera de Andrade, Telma Goncalves ^[2] ; Zangrossi, Jr., Hello ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Dept Biol Sci, Assis, SP - Brazil

• Document type: Journal article
• Source: Neuropharmacology; v. 148, p. 311-319, APR 2019.
• Web of Science Citations: 2

Abstract

The role of 5-HT2C receptors (5-HT2CRs) in the regulation of anxiety has been widely acknowledged. However, conflicting results have been reported on whether stimulation of these receptors increases or decreases anxiety. We here investigated the role of 5-HT2CRs of the dorsal hippocampus (DH) in the mediation of anxiety- or panic-associated defensive behaviors and in the anxiolytic effect of the tricyclic antidepressant imipramine. In the Vogel conflict test, administration of the mixed 5-HT2CR agonist mCPP into the DH of male Wistar rats was anxiogenic, whereas infusions of the more selective agonists MK-212 and RO-600175 were anxiolytic. The 5-HT2CR antagonist SB-242084, on the other hand, was anxiogenic. A sub-effective dose of this antagonist blocked the anxiolytic effect of RO-600175, but not the increase in anxiety observed with mCPP, indicating that the latter effect was not due to 5-HT2CR activation. In full agreement with these findings, MK-212 and RO-600175 in the DH also inhibited inhibitory avoidance acquisition in the elevated T-maze, whereas SB-242084 caused the opposite effect. None of these drugs interfered with escape expression in this test, which has been associated with panic. Chronic administration of imipramine (15 mg/kg, ip, 21 days) caused an anxiolytic effect in the elevated T-maze and light-dark transition tests, which was not blocked by previous infusion of SB-242084 into the DH. Therefore, facilitation of 5-HT2CR-mediated neurotransmission in the DH decreases the expression of anxiety-, but not panic-related defensive behaviors. This mechanism, however, is not involved in the anxiolytic effect caused by imipramine. (AU)

• FAPESP's process: 12/20016-6 - Involvement of 5-HT1A and 5-HT2C receptors of the dorsal hippocampus on the anxiolytic effect caused by antidepressant drugs
• Grantee: Ana Beatriz Sant Ana Do Nascimento
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/18437-7 - Investigation of the role of 5-HT1A receptors located in the lateral wings of the dorsal raphe nucleus on the panicolytic effect promoted by fluoxetine treatment
• Grantee: Heloísa Helena Vilela Costa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral