Facilitation of 5-HT(2A/2C)-mediated neurotransmission in the ventromedial hypothalamic nucleus decreases anxiety in the elevated T-maze.
Previous evidence has shown that facilitation of GABA/benzodiazepine-mediated neurotransmission in the ventromedial hypothalamus (VMH) inhibits both escape and inhibitory avoidance responses generated in the elevated T-maze test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Aside from GABA/benzodiazepine receptors, the VMH also contains a significant number of serotonin (5-HT) receptors, including 1A, 2A and 2C subtypes. The purpose of the present study was to investigate the effect of the activation of 5-HT(1A) and 5-HT(2A/2C) receptors in the VMH on defensive behavioral responses in rats submitted to the ETM. For that, male Wistar rats were treated intra-VMH with the 5-HT(1A) agonist 8-OH-DPAT, with the 5-HT(2A/2C) agonist DOI, with the 5-HT(2C) selective agonist MK-212, or with the 5-HT(2A/2C) antagonist ketanserin and 10 min after were submitted to the ETM. Results showed that both DOI and MK-212 significantly decreased avoidance measurements, an anxiolytic-like effect, without altering escape. 8-OH-DPAT and ketanserin were without effect, although the last drug attenuated the effects of DOI. None of the drugs altered locomotor activity in an open field. These results suggest that 5-HT(2A/2C) receptors of the VMH are involved in the regulation of inhibitory avoidance and might be of relevance to the physiopathology of generalized anxiety.
da Silva
E S
ES
Department of Biosciences, Federal University of São Paulo, Santos, Brazil.
Poltronieri
S C
SC
Nascimento
J O G
JO
Zangrossi
H
H
Viana
M B
MB
D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000517:prevention & control*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology
D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D018490:Serotonin Agents