Biomedical subjects

J S Carp

Publications and source records attributed to J S Carp.

26 records · Page 2Linked to original sources

PubMed1989

Memory traces in spinal cord produced by H-reflex conditioning: effects of post-tetanic potentiation.

Operant conditioning of the wholly spinal, largely monosynaptic triceps surae H-reflex in monkeys causes changes in lumbosacral spinal cord that persist after removal of supraspinal influence. We evaluated the interaction between post-tetanic potentiation and these memory traces. Animals in which the triceps surae H-reflex in one leg had been increased or decreased by conditioning were deeply anesthetized, and monosynaptic reflexes to L6-S1 dorsal root stimulation were recorded before and after tetanization from both legs for 3 days after thoracic cord transection. Animals remained anesthetized throughout and were sacrificed by overdose. Reflex asymmetries consistent with the effect of H-reflex conditioning were present after transection and persisted through the 3 days of study. Tetanization affected conditioned leg and control leg reflexes similarly. This finding suggests that, while post-tetanic potentiation and probably H-reflex conditioning alter Ia synaptic transmission, the two phenomena have different mechanisms.

Animals↗

PubMed1989

Prevention of phencyclidine-induced depression of the segmental reflex by L-3,4-dihydroxyphenylalanine in the rat spinal cord in vitro.

The interaction between phencyclidine (PCP) and the catecholamine precursor L-3,4-dihydroxyphenylalanine (DOPA) was studied in the isolated spinal cord from neonatal rats. PCP decreased the magnitude of the dorsal-ventral reflex and enhanced frequency-dependent depression of the reflex in a concentration-dependent manner. Although DOPA and DL-threo-3,4-dihydroxyphenylserine (a direct precursor for norepinephrine) had no effect on the reflex by themselves, DOPA, but not DL-threo-3,4-dihydroxyphenylserine prevented the depression of the reflex response by PCP in a concentration-dependent manner. Inhibition of aromatic-L-amino-acid decarboxylase (EC 4.1.1.2A) by m-hydroxybenzylhydrazine markedly attenuated the action of DOPA in preventing the depression caused by PCP. The dopamine receptor antagonists haloperidol and chlorpromazine blocked the action of DOPA, but the alpha and beta adrenergic receptor antagonists phentolamine and timolol, respectively, did not. In addition, prior treatment of neonatal rats with 6-hydroxydopamine diminished the ability of DOPA to prevent the depressant effect of PCP whereas partially attenuating the depressant effect of PCP alone. These results suggest that DOPA attenuated PCP-induced depression of spinal cord transmission through its conversion to dopamine rather than norepinephrine.

Animals↗

PubMed1986

Enhancement by serotonin of tonic vibration and stretch reflexes in the decerebrate cat.

The effects of pharmacological manipulation of serotonergic systems on spinal reflexes were determined in the unanesthetized decerebrate cat. The prolonged motor output that continues after cessation of high frequency longitudinal tendon vibration was strongly enhanced by the serotonin reuptake blocker fluoxetine and the serotonin precursor 5-hydroxytryptophan, and was decreased by the serotonin receptor antagonist methysergide. In addition, both dynamic and static stretch reflex stiffness was markedly increased by fluoxetine and 5-hydroxytryptophan, while methysergide produced a decrease in stretch reflex stiffness. These powerful effects on tonic vibration and stretch reflexes could not be explained by drug-induced alterations in muscle spindle primary afferent discharge. In light of other recent results on serotonin-mediated effects on motoneurons, we believe that the effects of these agents result from modification of an intrinsically mediated prolonged depolarization of spinal neurons. However, the possibility that these drugs modify longlasting discharge in associated interneuronal pathways cannot be ruled out.

Animals↗

PubMed1983

Electrophysiological and biochemical studies on enhancement of desensitization by phenothiazine neuroleptics.

The actions of the phenothiazines chlorpromazine, prochlorperazine, and trifluoperazine were studied on the acetylcholine receptor-ionic channel complex of frog and rat skeletal muscle and of Torpedo californica to determine their role in pharmacological desensitization and their interactions with different states of the receptor-ionic channel complex. The phenothiazines depressed the peak amplitude of spontaneous and evoked endplate currents while having negligible effect on the decay time constants. Mean channel lifetime and single channel conductance were not altered by these drugs. They also produced a frequency-dependent depression of the peak amplitude of endplate potentials evoked by repetitive microiontophoresis at the extrajunctional region. In addition, these drugs enhanced the ability of carbamoylcholine to displace 125I-labeled alpha-bungarotoxin from receptor-rich membrane preparations of T. californica when used in concentrations that had no effect on 125I-labeled alpha-bungarotoxin binding alone (10 microM). Similarly, the phenothiazines inhibited the binding of tritiated ionic channel ligands, such as phencyclidine and perhydrohistrionicotoxin, a process also enhanced by the presence of carbamoylcholine. These data suggest that the phenothiazines augment agonist-induced desensitization primarily by interacting with the receptor-ionic channel complex prior to channel opening.

Acetylcholine↗

PubMed1982

Dopamine receptor-mediated depression of spinal monosynaptic transmission.

The effects of the dopamine agonists apomorphine, lisuride and lergotrile were evaluated on cat spinal cord monosynaptic transmission by stimulating the dorsal root and recording the ventral root compound action potential. All 3 agonists decreased the area of the monosynaptic response. This effect was prevented by pretreatment with the dopamine antagonists haloperidol and metoclopramide, but not with the alpha-adrenergic antagonist phentolamine. These results suggest the existence of spinal cord dopamine receptors which can modulate motor output.

Action Potentials↗

PubMed1981

Modification of spinal cord transmission by an interaction of chlorpromazine and phenytoin.

Cat spinal cord monosynaptic activity during slow repetitive stimulation (0.2 Hz) and post-tetanic potentiation was used to evaluate the combination effects of phenytoin and chlorpromazine. The drug effects were compared in anesthetized cats with either high spinal transection or intact central nervous systems to determine whether the drugs were acting segmentally or suprasegmentally. When chlorpromazine and phenytoin were given in combination to intact animals, the depressant effect on the monosynaptic response was limited to 50% of control, which was not more than the maximum effect of either drug given alone. In spinal animals, chlorpromazine reversed the phenytoin-induced depression during 0.2 Hz stimulation, whereas only the effects of phenytoin on post-tetanic potentiation were evident after the drug combination. These results show that although phenytoin and chlorpromazine each have a depressant effect on spinal cord transmission, the combined effect is limited to a 50% decrease in intact animals. It is suggested that this occlusive drug effect demonstrates that the drug combination has a limited depressant action in the intact nervous system, an action which permits the expression of the effects of these drugs on the other elements of the reflex arc. Collectively, these actions of the drug combination are consistent with their known efficacy in treating certain cases of spasticity.

Animals↗

PubMed1979

Sensorimotor deficits produced by phenytoin and chlorpromazine in unanesthetized cats.

Unanesthetized adult cats were evaluated for suprasegmental reflex activity and motor skills before and after administration of chlorpromazine (0.0625--0.5 mg/kg) alone and in combination with phenytoin (20 mg/kg). The greatest deficits were seen in the tests of balance and corrdination in which half the animals failed to match their control responses after administration of chlorpromazine and phenytoin. The impairment was most noticeable with the most stringent test (walking a 4 cm wide beam), and the effects of the two drugs were additive. Although there was no effect of either drug on muscle strength, the two drugs in combination depressed the animals' motivational state, making them less willing to work against imposed loads. Neither drug, alone or in combination, altered responses to the flexor reflex, blind placing, the hopping response or visually aided placing. It is concluded that the effects of chlorpromazine and phenytoin on motor control are selective for the CNS loci which control balance and coordination. Although the two drugs produce additive responses, the deficits occur only at doses which are well above those needed for clinical efficacy and thus may not pose a problem in their long term clinical use.

Animals↗

PubMed1979

The effects of phenytoin on motor function in awake cats.

Adult cats were monitored for their performance of a variety of motor functions before and after acute administration of phenytoin (5, 10 or 20 mg/kg) in a schedule in which each animal received all drug doses. The only significant loss in motor function was balance and coordination. Half the animals could not balance or walk along a narrow-edged beam after 20 mg/kg of phenytoin although their performance was not impaired at lower drug doses or on wider surfaces. There were no effects of phenytoin on the righting reflex, flexor reflex, muscle strength, the hopping response, the blind placing response or visually aided placing. The data suggest that phenytoin has a selective effect on higher order neuronal systems involved with balance and locomotion rather than simple reflex pathways.

Animals↗