Benzodiazepines and synaptic processing in the spatial domain within the cat's primary somatosensory cortex.
In the primary somatosensory cortex of cats, the size of the receptive fields (RFs) of cutaneously responsive neurones is under the control of gamma-aminobutyric acid (GABA) mediated inhibition when the cells are situated in rapidly adapting (RA) background regions. Cells located in slowly adapting (SA) or low-velocity rapidly adapting (LVRA) background regions do not appear to be affected by GABA significantly in the spatial domain, although other response properties such as threshold and firing pattern are under the influence of bicuculline methiodide (BMI) sensitive processes. The GABA receptor is one component of the oligomeric complex that includes the benzodiazepine (Bzd) binding site, the barbiturate recognition site, and the Cl- ionophore. Owing to current debates about the possible existence of endogenous ligands of Bzd receptors, we have examined whether Bzd agonists, in addition to GABA and BMI, have RF-modulating actions on RA S1 neurones and have assessed the effectiveness of the Bzd antagonist, Ro 15-1788, in this experimental paradigm. Ro 15-1788 is an imidazobenzodiazepine that acts as a specific competitive antagonist of Bzds by exerting high-affinity interactions with that Bzd receptor through which anticonvulsant effects of flurazepam (flu) and diazepam are expressed. This has been shown previously in neurochemical, behavioral, neurological, and pharmacological studies. Ro 15-1788 has little or no affinity for nonneuronal binding sites in the CNS. Ro 15-1788 binding does not displace GABA from its own binding site but does compete for all major Bzd ligands that act as pharmacological agonists and inverse agonists of the Bzd receptor through which anticonvulsant and convulsant effects are expressed. Bzd agonists elevated the threshold for somatic activation, depressed spontaneous activity, and decreased RF size. One exception in this regard was midazolam, which sometimes decreased somatic thresholds and increased spontaneous discharges. These latter effects were reversed at higher doses of the agonist. BMI returned RFs to control sizes when the drug was administered concurrently with Bzd agonists, or it caused RFs to assume greater than normal sizes, depending on the strength of current ejecting the antagonist. Ro 15-1788 given alone decreased response thresholds, increased spontaneous firing, and sometimes enlarged RFs. This antagonist also reversed the RF size-decreasing action of flu, diazepam, and midazolam. Quantitative analyses of air-puffer responses evoked from low-threshold, S1 cells revealed that Bzds do not selectively attenuate spatial summation, but that they act preferentially in the surround, or in the peripheral, regions of cutaneous excitatory RFs.(ABSTRACT TRUNCATED AT 400 WORDS)
Oka
J I
JI
Department of Psychology, University of North Carolina, Greensboro 27412-5001.
Hicks
T P
TP
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002415:Cats; D003975:Diazepam / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D005476:Fluphenazine / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D010812:Physical Stimulation; D013003:Somatosensory Cortex / Q000187:drug effects*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D014151:Anti-Anxiety Agents; C017069:bicuculline methiodide; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D008874:Midazolam; D005476:Fluphenazine; D001640:Bicuculline