Pharmacological assessment of the freezing, antinociception, and exploratory behavior organized in the ventrolateral periaqueductal gray.
Opioid and serotonergic mechanisms of the ventrolateral periaqueductal gray (vlPAG) are recruited by conditioned freezing and antinociception. However, it is unclear whether freezing and antinociception induced by stimulation of the vlPAG are interrelated. To address this issue we looked at the effects of the opioid antagonist naltrexone, the 5-HT2 antagonist ketanserin, and the benzodiazepine agonist midazolam injected into the vlPAG on the freezing and antinociception induced by electrical stimulation of this region. This antinociception was evaluated by the tail-flick and formalin tests. To further characterize the involvement of the vlPAG in unconditioned fear, the effects of intra-vlPAG injections of midazolam on the exploratory behavior were also assessed in independent groups of rats submitted to the elevated plus-maze test (EPM). The data obtained showed that: (i) electrical stimulation of the vlPAG causes freezing blocked by midazolam but not by naltrexone and ketanserin; (ii) antinociception generated at the level of the vlPAG is inhibited by naltrexone, ketanserin, and midazolam; (iii) activation of benzodiazepine-mediated mechanisms in the vlPAG increased the exploratory behavior of rats in the closed arms but not the avoidance behavior of open arms of the EPM. Thus, freezing and antinociception generated in the vlPAG are dissociated pharmacologically. Whereas antinociception is a multimediated process sensitive to naltrexone, ketanserin, and midazolam, the freezing induced by vlPAG stimulation was reversed only by the benzodiazepine compound. As injections of midazolam into the vlPAG do not cause anxiolytic effects in the EPM, the aversive stimuli inherent of this test seem to bypass the vlPAG.
Laboratório de Psicobiologia, Departamento de Psicologia, FFCLRP-USP, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, Brazil.
Maria Cecília Zanoto
MC
De Luca-Vinhas
Carlos Eduardo
CE
Macedo
Marcus Lira
ML
Brandão
D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000009:adverse effects; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008845:Microinjections / Q000379:methods; D008874:Midazolam / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012702:Serotonin Antagonists / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D009292:Narcotic Antagonists; D012702:Serotonin Antagonists; D009271:Naltrexone; D007650:Ketanserin; D008874:Midazolam