Nociceptive vocalization response in guinea pigs modulated by opioidergic, GABAergic and serotonergic neurotransmission in the dorsal raphe nucleus.
The dorsal raphe nucleus (DRN) is involved in the control of several physiological functions, including nociceptive modulation. This nucleus is one of the main sources of serotonin to the CNS and neuromodulators such as opioids and GABA may be are important for its release. This study evaluated the influence of serotonergic, GABAergic and opioidergic stimulation, as well as their interactions in the DRN, on vocalization nociceptive response during a peripheral noxious stimulus application in guinea pigs. Morphine (1.1 nmol), bicuculline (0.50 nmol) and alpha-methyl-5-HT (1.6 nmol) microinjection on the DRN produces antinociception. The antinociception produced by morphine (1.1 nmol) and alpha-methyl-5-HT (1.6 nmol) into the DRN was blocked by prior microinjection of naloxone (0.7 nmol). The alpha-methyl-5-HT effect blocked by naloxone may indicate the existence of 5-HT2A receptors on enkephalinergic interneurons within the dorsal raphe. Pretreatment with muscimol (0.26 nmol) also prevented the antinociceptive effect caused by morphine (1.1 nmol) when administered alone at the same site, indicating an interaction between GABAergic and opioidergic interneurons. The antinociception produced by bicuculline (0.5 nmol) in the DRN was blocked by prior administration of 8-OH-DPAT (0.5 nmol), a 5-HT1A agonist. This may indicate that the 5-HT autoreceptor activation by 8-OH-DPAT at DRN effector neurons can oppose the bicuculline disinhibition effect applied to the same effectors. Thus, we suggest that 5-HT2 receptor activation in the DRN promotes endorphin/enkephalin release that may disinhibit efferent serotonergic neurons of this present structure by inhibiting GABAergic interneurons, resulting in antinociception.
Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14.049-900 Ribeirão Preto, SP, Brazil.
Mateus Dalbem
MD
Ferreira
Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14.049-900 Ribeirão Preto, SP, Brazil. Electronic address: lmdolive@fmrp.usp.br.
Leda
L
Menescal-de-Oliveira
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000502:physiology*; D009435:Synaptic Transmission; D014828:Vocalization, Animal / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000701:Analgesics, Opioid; D018755:GABA Agonists; D058787:GABA-A Receptor Antagonists; D009292:Narcotic Antagonists; D009118:Muscimol; D012701:Serotonin; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D001640:Bicuculline
Dorsal raphe nucleus; GABAergic system; Nociceptive vocalization response; Opioidergic system; Serotonin