Differential action of (-)-baclofen on the primary afferent depolarization produced by segmental and descending inputs.
The purpose of the present series of experiments was to analyze, in anesthetized and paralyzed cats, the effects of (-)-baclofen and picrotoxin on the primary afferent depolarization (PAD) generated in single Ib afferent fibers by either intraspinal microstimulation or stimulation of the segmental and descending pathways. PAD was estimated by recording dorsal root potentials and by measuring the changes in the intraspinal activation threshold of single Ib muscle afferent fibers. The PAD elicited by stimulation of group I muscle or cutaneous afferents was readily depressed and often abolished 20-40 min after the intravenous injection of 1-2 mg/kg (-)-baclofen. In contrast, the same amounts of (-)-baclofen produced a relatively small depression of the PAD elicited by stimulation of the brainstem reticular formation (RF). The monosynaptic PAD produced in single Ib fibers by intraspinal microstimulation within the intermediate nucleus was depressed and sometimes abolished following the i.v. injections of 1-2 mg/kg (-)-baclofen. Twenty to forty minutes after the i.v. injection of picrotoxin (0.5-1 mg/kg), there was a strong depression of the PAD elicited by stimulation of muscle and cutaneous afferents as well as of the PAD produced by stimulation of the RF and the PAD produced by intraspinal microstimulation. The results obtained suggest that, in addition to its action on primary afferents, (-)-baclofen may depress impulse activity and/or transmitter release in a population of last-order GABAergic interneurons that mediate the PAD of Ib fibers. The existence of GABAb autoreceptors in last-order interneurons mediating the PAD may function as a self-limiting mechanism controlling the synaptic efficacy of these interneurons.
Quevedo
J
J
Department of Physiology, Biophysics and Neurosciences, Centro de Investigación y de Estudios Avanzados del IPN, México D.F.
Eguibar
J R
JR
Jiménez
I
I
Rudomin
P
P
D000758:Anesthesia; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002415:Cats; D004558:Electric Stimulation; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012154:Reticular Formation / Q000166:cytology / Q000502:physiology; D012867:Skin / Q000294:innervation; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D013569:Synapses / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D001418:Baclofen; D009467:Neuromuscular Depolarizing Agents; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid