title: Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters.
abstract: This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an important role in the regulation of aversive responses in the periaqueductal gray (PAG). Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1) receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA) that control PAG activity. We propose that they exert a 'fine-tuning' regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brasil.
authors.forename: M V
authors.initials: MV
authors.lastname: Fogaça
authors.forename: S F
authors.initials: SF
authors.lastname: Lisboa
authors.forename: D C
authors.initials: DC
authors.lastname: Aguiar
authors.forename: F A
authors.initials: FA
authors.lastname: Moreira
authors.forename: F V
authors.initials: FV
authors.lastname: Gomes
authors.forename: P C
authors.initials: PC
authors.lastname: Casarotto
authors.forename: F S
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology*; D001095:Arachidonic Acids / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology / Q000502:physiology; D004924:Escape Reaction / Q000502:physiology*; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D010487:Periaqueductal Gray / Q000378:metabolism / Q000502:physiology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D018377:Neurotransmitter Agents; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D009569:Nitric Oxide; C078814:anandamide