Panicolytic-like effect induced by the stimulation of GABAA and GABAB receptors in the dorsal periaqueductal grey of rats.
Activation of GABA(A) and benzodiazepine receptors within the dorsal periaqueductal grey inhibits the escape behaviour evoked by the electrical stimulation of this midbrain area, a defensive reaction that has been related to panic. Nevertheless, there is no evidence indicating whether the same antiaversive effect is also observed in escape responses evoked by species-specific threatening stimuli. In the present study, male Wistar rats were injected intra-dorsal periaqueductal grey with the benzodiazepine receptor agonist midazolam (10, 20 and 40 nmol), the GABA(A) receptor agonist muscimol (2, 4 and 8 nmol), the GABA(B) receptor agonist baclofen (2, 4 and 8 nmol), or with the benzodiazepine inverse agonist FG 7142 (20, 40 and 80 pmol) and tested in an ethologically-based animal model of anxiety, the elevated T-maze. Besides escape, this test also allows the measurement of inhibitory avoidance which has been related to generalised anxiety disorder. Midazolam, muscimol and baclofen impaired escape, a panicolytic-like effect, without altering inhibitory avoidance. FG 7142, on the other hand, facilitated both avoidance and escape reactions, suggesting an anxiogenic and panicogenic-like effect, respectively. The data suggest that GABA(A)/benzodiazepine and GABA(B) receptors within the dorsal periaqueductal grey are involved in the control of escape behaviour and that a failure in this regulatory mechanism may be of importance in panic disorder.
Bueno
Cíntia H
CH
Laboratório de Psicofarmacologia, Departamento de Psicologia e Educação, FFCLRP, Universidade de São Paulo, 14040-901, Ribeirão Preto, São Paulo, Brazil.
Zangrossi
Hélio
H
Nogueira
Regina L
RL
Soares
Vanessa P
VP
Viana
Milena B
MB
D000704:Analysis of Variance; D000818:Animals; D001008:Anxiety Disorders / Q000503:physiopathology / Q000517:prevention & control; D001362:Avoidance Learning / Q000187:drug effects; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D016584:Panic Disorder / Q000503:physiopathology* / Q000517:prevention & control; D010487:Periaqueductal Gray / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*
D002243:Carbolines; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; C035874:FG 7142; D001418:Baclofen; D008874:Midazolam