Cannabinoid modulation of predator fear: involvement of the dorsolateral periaqueductal gray.
The present study investigated the effects of systemic or intra-dorsolateral periaqueductal gray (dlPAG) administration of CB1 agonists on behavioural changes induced in rats by predator (a live cat) exposure, a model of panic responses. Since nitric oxide (NO) and cannabinoid neurotransmission are proposed to interact in the dlPAG to modulate defensive responses, we also investigated if NO is involved in the biphasic effects of anandamide (AEA) injected into the dlPAG. The results showed that systemic administration of WIN55,212-2 or intra-dlPAG AEA attenuated the defensive behaviours caused by cat exposure. Both compounds produced biphasic curves. The cannabinoid receptor type 1 (CB1) antagonist AM251 prevented the panicolytic effect of AEA whereas a neuronal NOS inhibitor turned the ineffective high dose of AEA into an effective one. These results suggest that modulation of the cannabinoid system could be a target in the treatment of panic disorders. However, the biphasic effects of these compounds could limit their therapeutic potential.
Department of Pharmacology, School of Medicine of Ribeirão Preto, Ribeirão Preto, SP, and Centre for Interdisciplinary Research on Applied Neurosciences (NAPNA),University of São Paulo,Brazil.
S F
SF
Lisboa
Department of Pharmacology, School of Medicine of Ribeirão Preto, Ribeirão Preto, SP, and Centre for Interdisciplinary Research on Applied Neurosciences (NAPNA),University of São Paulo,Brazil.
L H A
LH
Camargo
Department of Pharmacology, School of Medicine of Ribeirão Preto, Ribeirão Preto, SP, and Centre for Interdisciplinary Research on Applied Neurosciences (NAPNA),University of São Paulo,Brazil.
A C
AC
Magesto
Department of Pharmacology, School of Medicine of Ribeirão Preto, Ribeirão Preto, SP, and Centre for Interdisciplinary Research on Applied Neurosciences (NAPNA),University of São Paulo,Brazil.
L B M
LB
Resstel
Department of Pharmacology, School of Medicine of Ribeirão Preto, Ribeirão Preto, SP, and Centre for Interdisciplinary Research on Applied Neurosciences (NAPNA),University of São Paulo,Brazil.
F S
FS
Guimarães
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008845:Microinjections; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011235:Predatory Behavior; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
D001095:Arachidonic Acids; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D009025:Morpholines; C000596751:N5-(imino(propylamino)methyl)ornithine; D009281:Naphthalenes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009952:Ornithine; D052248:Nitric Oxide Synthase Type I; C078814:anandamide