title: Glutamate/GABA balance in ACC modulates the nociceptive responses of vocalization: an expression of affective-motivational component of pain in guinea pigs.
abstract: Evidence corroborates the role of the anterior cingulate cortex (ACC) in the modulation of cognitive and emotional functions. Its involvement in the motivational-affective component of pain has been widely investigated using different methods to elucidate the specific role of different neurotransmitter systems. We used the peripheral noxious stimulus-induced vocalization algesimetric test to verify glutamatergic and GABAergic neurotransmission in the guinea pig ACC. Microinjection of homocysteic acid (DLH; 30 nmol) in the left guinea pig ACC increased the amplitude of vocalizations (pronociception) compared to controls injected with saline. Moreover, microinjection of MK-801 (3.6 nmol), an NMDA receptor antagonist, did not alter the amplitude of vocalizations, but its microinjection prior to DLH prevented the increase in vocalizations induced by this drug. Regarding the GABAergic system, blockade of GABAA receptors with bicuculline (1 nmol) increased the amplitude of vocalizations, while three different doses of the GABAA agonist muscimol (0.5, 1 and 2 nmol) did not influence nociceptive vocalization responses. Finally, a combination of MK-801 (3.6 nmol) and muscimol (1 nmol) reduced the amplitude of vocalizations (antinociception), suggesting that a combination of glutamate and GABA in the ACC modulates the expression of affective-motivational pain response. We suggest that activation of NMDA receptors or blockade of GABAergic neurotransmission promotes pronociception and that the antinociceptive effect of muscimol depends on the blockade of NMDA receptors.
authors.affiliation: Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14.049-900 Ribeirão Preto, SP, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Zugaib
authors.affiliation: Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14.049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Márcio Ramos
authors.initials: MR
authors.lastname: Coutinho
authors.affiliation: Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14.049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Mateus Dalbem
authors.initials: MD
authors.lastname: Ferreira
authors.affiliation: 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.
authors.forename: Leda
authors.initials: L
authors.lastname: Menescal-de-Oliveira
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D006710:Homocysteine; C007956:homocysteic acid; D009118:Muscimol; D018698:Glutamic Acid; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D001640:Bicuculline
keywords: GABA; Glutamate; Guinea pig; Nociception; Vocalization