Changes in rectal temperature and ECoG spectral power of sensorimotor cortex elicited in conscious rabbits by i.c.v. injection of GABA, GABA(A) and GABA(B) agonists and antagonists.
1. In order to ascertain whether both GABA(A) and GABA(B), or only GABA(B) receptors, directly modulate thermoregulation in conscious rabbits, GABA(A)/GABA(B) agonist and antagonist agents were injected intracerebroventricularly in conscious rabbits while monitoring changes in rectal temperature (RT), gross motor behaviour (GMB) and electrocorticogram (ECoG) power spectra (ps) from sensorimotor cortices. 2. GABA (48 micromol), nipecotic acid (50 nmol), THIP (60 nmol), muscimol (18 nmol) and baclofen (8 nmol) induced hypothermia (-deltaRTmax values of 1.70+/-0.1, 1.4+/-0.2, 1.0+/-0.4, 1.1+/-0.2 and 1.6+/-0.3 degrees C, respectively), accompanied by inhibition of GMB and ECoG synchronization. THIP increased ps at delta frequency band (1.1-3.3 Hz), while GABA, nipecotic acid, muscimol and baclofen did the same at both delta and (4.6-6.5 Hz) frequency bands. ECoG ps changes were concomitant or even preceded hypothermia. 3. Bicuculline (1.8 nmol) induced hyperthermia (deltaRTmax 1.2+/-0.5 degrees C) and slight excitation of GMB, while CGP35348 (1.2 micromol) did not affect RT nor GMB. Both compounds did not affect ECoG ps. 4. Bicuculline potentiated muscimol-induced hypothermia, inhibition of GMB and synchronization of ECoG, while CGP35348 fully antagonized these effects. 5. In conclusion, the present results, while confirming the prevailing role of GABA(B), also outline a direct involvement of GABA(A) receptors in the central mechanisms of thermoregulation. Ascending inhibition towards discrete cortical areas controlling muscular activity and thermogenesis may result from GABA receptor activation in neurones proximal to the ventricles, thus contributing to hypothermia, although hypothermia-induced reduction of neuronal activity of these cortical areas cannot be ruled out.
Frosini
Maria
M
Istituto di Scienze Farmacologiche, Università di Siena, Nuovo Polo Scientifico di S. Miniato, Via A. Moro 2, lotto C, Siena 53100, Italy. frosinim@unisi.it
Valoti
Massimo
M
Sgaragli
Giampietro
G
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000493:pharmacokinetics; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000008:administration & dosage / Q000493:pharmacokinetics; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D018755:GABA Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018756:GABA Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007276:Injections, Intraventricular; D007555:Isoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D020547:Lateral Ventricles / Q000187:drug effects; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000493:pharmacokinetics; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D011963:Receptors, GABA-A / Q000187:drug effects; D018080:Receptors, GABA-B / Q000187:drug effects; D012007:Rectum; D013003:Somatosensory Cortex / Q000187:drug effects* / Q000502:physiology
D018755:GABA Agonists; D018756:GABA Antagonists; D007555:Isoxazoles; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C030278:nipecotic acid; D009118:Muscimol; D001418:Baclofen; C015542:gaboxadol; D001640:Bicuculline