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

Abstract

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.

Figure 1

Time course of the effects elicited by i.c.v. injection of pyrogen-free water (vehicle, n=6), GABA (48 μmol, n=6) and nipecotic acid (50 nmol, n=6) (panel a); THIP (60 nmol, n=4), muscimol (18 nmol, n=5) and R(−)baclofen (8 nmol, n=6) (panel b) on rabbit RT. Data are reported as mean±s.e.m. of RT changes. The arrow indicates time of i.c.v. injection.

Figure 2

Time course of the effects elicited by i.c.v. injection of pyrogen-free water (vehicle, n=6), muscimol alone (18 nmol, n=5, data from Figure 1), muscimol+0.2 nmol bicuculline (n=4), muscimol+1.8 nmol bicuculline (n=4) (panel a); pyrogen-free water (vehicle, n=6), muscimol+0.4 μmol CGP35348 (n=4), muscimol+1.2 μmol CGP35348 (n=4) (panel b); bicuculline (1.8 nmol, n=4) and CGP35348 (1.2 μmol, n=4) (panel c). Data are reported as mean±s.e.m. of RT changes. To improve the clarity, the s.e.m. of RT values of muscimol in panel a are not depicted. The arrow indicates time of i.c.v. injection.

Figure 3

Changes in ECoG power spectrum induced by i.c.v. injection of GABA, GABA_A/GABA_B agonists and antagonists. Values of energy power at each frequency band were firstly normalized by calculating the ratio of mean spectral power obtained following the injection of drug vs the mean spectral power obtained following administration of vehicle. The time course of changes in ECoG power (expressed as % over controls) at each frequency band gave areas under the curve (AUC_{(0–24 h)} after the injection) reported as mean±s.e.m. values (n=4–6). The comparison between AUC_{(0–24 h)} post-drug and AUC_{(0–24 h)} post-vehicle was performed using ANOVA followed by post hoc Dunnett's test. A P-value <0.05 was considered significant. ^**P<0.01; ^*P<0.05.

Figure 4

Changes in ECoG power spectrum following drug treatments which induced hypothermia. Energy power values at each frequency band were normalized as the ratio of mean spectral power post-drug at the peak of hypothermia vs the mean spectral power obtained following administration of vehicle at the same frequency. Data are reported as mean±s.e.m. values (n=4–6). The comparison between ECoG changes of different drugs was performed using ANOVA followed by post hoc Dunnett's test. A P-value <0.05 was considered significant. ^**P<0.01; ^*P<0.05.

Figure 5

Time course of the effects elicited by muscimol (18 nmol, n=5) on ECoG energy power at single frequency bands and on RT. Data are reported as mean±s.e.m. ECoG values were normalized by expressing them as the percent value of the average ECoG power density at the same frequency band, recorded after i.c.v. injection of the vehicle during the same period of time (horizontal line; for further details, see Methods).

Figure 6

Time course of the effects elicited by GABA (48 μmol, n=6) on ECoG energy power at single frequency bands and on RT. Data are reported as mean±s.e.m. ECoG values were normalized by expressing them as the percent value of the average ECoG power density at the same frequency band, recorded after i.c.v. injection of the vehicle during the same period of time (horizontal line; for further details, see Methods).