strychnine and phaclofen

We studied the regulation of spontaneous activity in the embryonic (day 10-11) chick spinal cord. After bath application of either an excitatory amino acid (AP-5 or CNQX) and a nicotinic cholinergic (DHbetaE or mecamylamine) antagonist, or glycine and GABA receptor (bicuculline, 2-hydroxysaclofen, and strychnine) antagonists, spontaneous activity was blocked for a period (30-90 min) but then reappeared in the presence of the drugs. The efficacy of the antagonists was assessed by their continued ability to block spinal reflex pathways during the reappearance of spontaneous activity. Spontaneous activity ceased over the 4-5 hour monitoring period when both sets of antagonists were applied together. After application of glycine and GABA receptor antagonists, the frequency of occurrence of spontaneous episodes slowed and became highly variable. By contrast, during glutamatergic and nicotinic cholinergic blockade, the frequency of occurrence of spontaneous episodes initially slowed and then recovered to stabilize near the predrug level of activity. Whole-cell recordings made from ventral spinal neurons revealed that this recovery was accompanied by an increase in the amplitude of spontaneously occurring synaptic events. We also measured changes in the apparent equilibrium potential of the rhythmic, synaptic drive of ventral spinal neurons using voltage or discontinuous current clamp. After excitatory blockade, the apparent equilibrium potential of the rhythmic synaptic drive shifted approximately 10 mV more negative to approximately -30 mV. In the presence of bicuculline, the apparent equilibrium potential of the synaptic drive shifted toward the glutamate equilibrium potential. Considered with other evidence, these findings suggest that spontaneous rhythmic output is a general property of developing spinal networks, and that GABA and glycinergic networks alter their function to compensate for the blockade of excitatory transmission.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Action Potentials; Animals; Baclofen; Bicuculline; Chick Embryo; Cholinergic Antagonists; Dihydro-beta-Erythroidine; Evoked Potentials; Excitatory Amino Acid Antagonists; GABA Antagonists; GABA-A Receptor Antagonists; Glycine; Glycine Agents; Mecamylamine; Motor Neurons; Neuronal Plasticity; Neurotransmitter Agents; Nicotinic Antagonists; Periodicity; Spinal Cord; Strychnine

Stimulation of the amygdala in rats is known to elicit increases in heart rate (HR) and blood pressure (BP) as well as locomotor activity associated with emotional arousal. The present study was conducted to localize and characterize the role of the GABA system of the amygdala in regulating these cardiovascular responses. Male Sprague-Dawley rats with arterial catheters placed for physiological measurements were implanted with chronic microinjection cannulae in the anterior basolateral (BLA) and central (Ce) amygdaloid nuclei under pentobarbital anesthesia. After recovering, rats were microinjected bilaterally with saline (250 nl) and bicuculline methiodide (BMI, 5-25 ng/250 nl), a selective GABAA antagonist. Microinjection of BMI in the BLA caused significant increases in HR and BP as well as locomotor stimulation while saline had no effect. The cardiovascular response to BMI was blocked by pentobarbital anesthesia. Microinjection of equimolar concentrations of (+)-baclofen HCl (GABAB agonist), phaclofen (GABAB antagonist), or strychnine (glycine antagonist) into the BLA or BMI into the Ce had no significant cardiovascular effects. The cardiovascular effects of BMI injection in the BLA does not appear to be secondary to generalized seizure activity. These results suggest that endogenous GABA, acting on GABAA receptors in the region of the BLA, may be involved in cardiovascular regulation.

Topics: Amygdala; Analysis of Variance; Anesthesia, General; Animals; Baclofen; Bicuculline; Blood Pressure; Consciousness; Dose-Response Relationship, Drug; Electroencephalography; Heart Rate; Hippocampus; Male; Microinjections; Motor Activity; Rats; Rats, Inbred Strains; Receptors, GABA-A; Strychnine; Temporal Lobe

Excitatory amino acid agonists increased the probability of discharge of ventral horn cells in slices of spinal cord isolated from adult rats. The order of potency for the facilitatory action was kainate greater than quisqualate greater than N-methyl-D-aspartate (NMDA) greater than L-glutamate greater than L-aspartate. (+/-)-2-Amino-5-phosphonovalerate (2-APV) markedly reduced the facilitatory effects produced by L-aspartate and NMDA, and slightly decreased the effect produced by L-glutamate but did not alter the effect of kainate. Inhibitory amino acid agonists decreased the probability of cell discharge. The order of potency for the inhibitory action was (-)-baclofen greater than muscimol greater than glycine = GABA. The effects produced by glycine, muscimol or GABA and (-)-baclofen were selectively reduced by strychnine, bicuculline and phaclofen, respectively. This type of preparation may be useful for in vitro pharmacological studies on the action of transmitters and drugs on ventral horn cells in the adult spinal cord.

Topics: Action Potentials; Amino Acids; Animals; Anterior Horn Cells; Baclofen; Bicuculline; gamma-Aminobutyric Acid; Glycine; In Vitro Techniques; Male; Muscimol; Rats; Rats, Inbred Strains; Strychnine; Synapses