PubMed · 7309254
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T H Corbett. 1981. Carcinogenesis.. https://doi.org/10.1097/00004311-198119040-00008
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gamma-Hydroxybutyric acid (GHB), a naturally occurring analog of GABA, induces absence-like seizures in rats. We characterized the interaction of 3alpha-hydroxy steroids, alphaxalone and tetrahydrodeoxycorticosterone (which are potent modulators of GABAA receptors) with GHB binding sites in rat brain cortical membranes. The steroids inhibited [3H]GHB binding in a dose-dependent fashion (IC50 approximately 1 microM). Neither bicuculline nor GABA altered the dose-response of steroids in the [3H]GHB assay, suggesting that there was no GABAA component involved in the steroid-inhibition of [3H]GHB binding. Also, non 3alpha-hydroxy steroids were inactive in displacing [3H]GHB. Because GHB-induced absence seizures evolve most readily from layers I-IV of frontoparietal cortex and thalamic relay nuclei, we determined if the interaction of steroids with GHB binding sites in layers I-IV of frontoparietal cortex and thalamic relay nuclei was altered during GHB-induced absence seizures. We found that during GHB-seizures steroid-inhibition of [3H]GHB binding was increased selectively in thalamic relay nuclei but not in the layers I-IV of frontoparietal cortex or any other brain regions tested. This increase in steroid-inhibition of [3H]GHB binding in thalamus was apparent about 30 min after the onset of seizures, but not at the seizure-onset. As the seizures dissipated, the IC50 values for steroids rose to the pre-seizure level. These data suggest that the enhancement in steroid-inhibition of [3H]GHB binding in thalamic relay nuclei observed during GHB-seizures was caused by absence seizures.
To investigate the possible mechanisms by which neurons in the caudate-putamen (CPu) and globus pallidus (GP) participate in pain and nociception, the present study characterized the response properties of CPu and GP neurons to non-noxious and noxious thermal stimuli in anesthetized rats. Nociceptive CPu and GP neurons were capable of encoding noxious thermal stimuli and 79% of these thermally responsive neurons also responded to noxious mechanical stimuli. Thermally responsive neurons were activated during the phasic rise and fall of the thermal shift in addition to the plateau temperature. The ability of CPu and GP neurons to encode noxious thermal stimulation intensity and respond during the dynamic phase of the stimulus suggests that these neurons may contribute to the behavioral response to minimize bodily harm.
Ethanol at concentration of 200 mM induces anesthesia in experimental animals and depresses neurotransmission in isolated spinal cords. To determine whether actions on primary afferent nerve terminals contribute to ethanol's depressant effects on spinal cord, a study was undertaken to test whether ethanol blocks sodium currents (I(Na)) in dorsal root ganglion neurons (DRGn). Whole-cell patch clamp was used to examine I(Na) in DRGn isolated from 1- to 15-day-old rats. At a holding potential of -80 mV ethanol (200 mM) decreased peak tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) I(Na) by 19.0% +/- 2.7 (mean +/- SEM) and 8.5% +/- 2.2, respectively. Maximal available I(Na) was reduced to 82 +/- 4% (TTX-R) and 93 +/- 1% (TTX-S) of control. Steady-state inactivation curves were shifted in the hyperpolarizing direction by 2.1 +/- 0.2 mV (TTX-R) and 1.1 +/- 0.1 mV (TTX-S). At prepulse potentials of -30 mV (TTX-R) and -70 mV (TTX-S), these shifts contributed an additional 17 +/- 1% (TTX-R) and 7 +/- 1% (TTX-S) reduction in available I(Na). Ethanol thus selectively induced both voltage-independent and voltage-dependent block of TTX-R I(Na) in DRGn. Because DRGn TTX-R sodium channels are associated with small-diameter primary afferent fibers, these results are consistent with a role for ethanol actions on sodium channels in depression of nociceptive-related neurotransmission in spinal cord.