L-allylglycine dissociates the neural substrates of fear in the periaqueductal gray of rats.
The dorsal (dPAG) and ventral (vPAG) regions of the periaqueductal gray are well known to contain the neural substrates of fear and anxiety. Chemical or electrical stimulation of the dPAG induces freezing, followed by a robust behavioral reaction that has been considered an animal model of panic attack. In contrast, the vPAG is part of a neural system, in which immobility is the usual response to its stimulation. The defense reaction induced by the stimulation of either region is accompanied by antinociception. Although GABAergic mechanisms are known to exert tonic inhibitory control on the neural substrates of fear in the dPAG, the role of these mechanisms in the vPAG is still unclear. The present study examined defensive behaviors and antinociception induced by microinjections of an inhibitor of gamma-aminobutyric acid synthesis, L-allylglycine (l-AG; 1, 3, and 5 microg/0.2 microl), into either the dPAG or vPAG of rats subjected to the open field and tail-flick tests. Passive or tense immobility was the predominant behavior after L-AG (1 or 3 microg) microinjection into the vPAG and dPAG, respectively, which was replaced with intense hyperactivity, including jumps or rearings, after injections of a higher dose (5 microg/0.2 microl) into the dPAG or vPAG. Moreover, whereas intra-dPAG injection of 3 microg L-AG produced intense antinociception, only weak antinociception was induced by intra-vPAG injections of 5 microg L-AG. These findings suggest that GABA mechanisms are involved in the mediation of antinociception and behavioral inhibition to aversive stimulation of the vPAG and exert powerful control over the neural substrates of fear in the dPAG to prevent a full-blown defense reaction possibly associated with panic disorder.
Cunha
Joice Maria
JM
Instituto de Neurociências e Comportamento-INeC, Campus USP, 14040-901 Ribeirão Preto, SP, Brazil.
Zanoveli
Janaina Menezes
JM
Ledvinka-Filho
Eduardo
E
Brandão
Marcus Lira
ML
D000501:Allylglycine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002404:Catheterization; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects* / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018756:GABA Antagonists; D000501:Allylglycine