Actions of (-)-baclofen on rat dorsal horn neurons.
The actions of a gamma-aminobutyric acid B (GABAB) agonist, (-)-baclofen, on the electrophysiological properties of neurons and synaptic transmission in the spinal dorsal horn (laminae I-IV) were examined by using intracellular recordings in spinal cord slice from young rats. In addition, the effects of baclofen on the dorsal root stimulation-evoked outflow of glutamate and aspartate from the spinal dorsal horn were examined by using high performance liquid chromatography (HPLC) with flourimetric detection. Superfusion of baclofen (5 nM to 10 microM) hyperpolarized, in a stereoselective and bicuculline-insensitive manner, the majority (86%) of tested neurons. The hyperpolarization was associated with a decrease in membrane resistance and persisted in a nominally zero-Ca2+, 10 mM Mg(2+)- or a TTX-containing solution. Our findings indicate that the hyperpolarizing effect of baclofen is probably due to an increase in conductance to potassium ions. Baclofen decreased the direct excitability of dorsal horn neurons, enhanced accommodation of spike discharge, and reduced the duration of Ca(2+)-dependent action potentials. Baclofen depressed, or blocked, excitatory postsynaptic potentials evoked by electrical stimulation of the dorsal roots. Spontaneously occurring synaptic potentials were also reversibly depressed by baclofen. Whereas baclofen did not produce any consistent change in the rate of the basal outflow of glutamate and aspartate, the stimulation-evoked release of the amino acids was blocked. The present results suggest that baclofen, by activating GABAB receptors, may modulate spinal afferent processing in the superficial dorsal horn by at least two mechanisms: (1) baclofen depresses excitatory synaptic transmission primarily by a presynaptic mechanism involving a decrease in the release of excitatory amino acids, and (2) at higher concentrations, the hyperpolarization and increased membrane conductance may contribute to the depressant effect of baclofen on excitatory synaptic transmission in the rat spinal dorsal horn.
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50010.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D005971:Glutamates; D001224:Aspartic Acid; D018698:Glutamic Acid; D012964:Sodium; D001418:Baclofen; D002118:Calcium