Stimulation of 5-HT1A or 5-HT2A receptors in the ventrolateral periaqueductal gray causes anxiolytic-, but not panicolytic-like effect in rats.
Evidences from studies using electrical or chemical stimulation of the midbrain periaqueductal gray (PAG) suggest that whereas the dorsal PAG is critical for the regulation of panic-related defensive behaviors, the ventrolateral PAG (vlPAG) modulates generalized anxiety-related responses. In the present study we evaluated whether the activation of 5-HT1A and 5-HT2A/2C receptors in the ventrolateral column of the periaqueductal gray (vlPAG) causes differential effects on an anxiety- and a panic-related defensive behavior, respectively, inhibitory avoidance and escape, in male Wistar rats submitted to the elevated T-maze. Our results showed that intra-vlPAG injection of the endogenous agonist serotonin, the 5-HT1A/7 agonist 8-OH-DPAT or 5-HT2A/2C agonist DOI impaired the acquisition of inhibitory avoidance, without interfering with escape performance. The same selective anxiolytic effect was also observed after local administration of the benzodiazepine receptor agonist midazolam. Moreover, as shown by the results of antagonism studies, 5-HT2A receptors are recruited for the anxiolysis caused by serotonin and DOI, while 5-HT1A receptors account for the effect of 8-OH-DPAT. In conclusion, our data show that the activation of 5-HT1A and 5-HT2A receptors in the vlPAG affects defensive responses related to generalized anxiety, but not panic disorder.
de Paula Soares
Vanessa
V
Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, CEP: 14049-900 Ribeirão Preto, Brazil.
Zangrossi
Hélio
H
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism*; 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; D008874:Midazolam / Q000627:therapeutic use; D016584:Panic Disorder / Q000188:drug therapy / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018709:Statistics, Nonparametric
D014151:Anti-Anxiety Agents; D044402:Receptor, Serotonin, 5-HT2A; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D008874:Midazolam