Periaqueductal gray metabotropic glutamate receptor subtype 7 and 8 mediate opposite effects on amino acid release, rostral ventromedial medulla cell activities, and thermal nociception.
The current study has investigated the involvement of periaqueductal gray (PAG) metabotropic glutamate subtype 7 and 8 receptors (mGluR(7) and mGluR(8)) in modulating rostral ventromedial medulla (RVM) ongoing and tail flick-related on and off cell activities. Our study has also investigated the role of PAG mGluR(7) on thermoceptive threshold and PAG glutamate and GABA release. Intra-ventrolateral PAG (S)-3,4-dicarboxyphenylglycine [(S)-3,4-DCPG (2 and 4 nmol/rat)] or N,N(I)-dibenzhydrylethane-1,2-diamin dihydrochloride (AMN082, (1 and 2 nmol/rat), selective mGluR(8) and mGluR(7) agonists, respectively, caused opposite effects on the ongoing RVM on and off cell activities. Tail flick latency was increased or decreased by (S)-3,4-DCPG or AMN082 (2 nmol/rat), respectively. (S)-3,4-DCPG reduced the pause and delayed the onset of the off cell pause. Conversely, AMN082 increased the pause and shortened the onset of off cell pause. (S)-3,4-DCPG or AMN082 did not change the tail flick-induced onset of on-cell peak firing. The tail flick latency and its related electrophysiological effects induced by (S)-3,4-DCPG or AMN082 were prevented by (RS)-alpha-methylserine-o-phosphate (100 nmol/rat), a group III mGluR antagonist. Intra-ventrolateral PAG perfusion with AMN082 (10 and 25 microM), decreased thermoceptive thresholds and glutamate extracellular levels. A decrease in GABA release was also observed. These results show that stimulation of PAG mGluR(8) or mGluR(7) could either relieve or worsen pain perception. The opposite effects on pain behavior correlate with the opposite roles played by mGluR(7) and mGluR(8) on glutamate and GABA release and the ongoing and tail flick-related activities of the RVM on and off cells.
Marabese
Ida
I
Dept of Experimental Medicine, Sect of Pharmacology L Donatelli, Faculty of Medicine and Surgery, Second University of Naples, Via Constantinopoli, Naples, Italy.
Rossi
Francesca
F
Palazzo
Enza
E
de Novellis
Vito
V
Starowicz
Katarzyna
K
Cristino
Luigia
L
Vita
Daniela
D
Gatta
Luisa
L
Guida
Francesca
F
Di Marzo
Vincenzo
V
Rossi
Francesco
F
Maione
Sabatino
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology*; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C110733:3,4-dicarboxyphenylglycine; D001559:Benzhydryl Compounds; D001565:Benzoates; D018690:Excitatory Amino Acid Agonists; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; C111435:metabotropic glutamate receptor 8; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine