Differential effects of delta-9-tetrahydrocannabinol and its 11-hydroxy metabolite on sodium current in neuroblastoma cells.

Whole-cell voltage-clamp techniques were used to study the comparative effects of delta-9-tetrahydrocannabinol (THC) and its principal metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC), on the voltage-gated sodium current in neuroblastoma cells. The parent compound markedly depressed the inward sodium current with minimal reduction of the outward current, demonstrating that the effects of the drug were related to the membrane potential. In addition, THC reduced the reversal potential, indicating that the drug modified the ion selectivity of the channel.

DNQX blockade of amphetamine behavioral sensitization.

The role of the N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptors in the mechanism of behavioral sensitization to amphetamine-induced sterotypy was investigated in mice. The results confirm previous observations that NMDA antagonists can block the induction of the phenomenon but not the expression; in contrast, DNQX, a non-NMDA receptor antagonist, can block both the induction and the expression of the sensitization. The differential effects of the two classes of antagonists suggest that the induction and the expression are the result of different mechanisms, both of which involve the EAA system.

Calcium channel blockers and excitatory amino acids.

The calcium channel blockers (CCB), diltiazem, verapamil and nifedipine, antagonize in mice both N-methyl-DL-aspartate- (NMDLA) and kainate-induced convulsions, which were not affected by carbamazepine and ethosuximide. The CCB, on the other hand, were ineffective against convulsions induced by bicuculline, pentylenetetrazol and electroshock. The results suggest that the CCB may be efficacious in the treatment of those neurodegenerative diseases putatively caused by the excitatory amino acids.

Calcium channel blockers and behavioral sensitization.

Behavioral sensitization to amphetamine-induced stereotypy was previously shown to consist of two separable phenomena, induction and expression, both of which involve the excitatory amino acids (EAA). In the present experiments, the calcium channel blockers (CCB), nifedipine, diltiazem and verapamil, were shown to block both phenomena; these results are similar to those reported earlier for DNQX, an antagonist of the non-N-methyl-D-aspartate receptors for the EAA. The CCB, like DNQX, affect only that percentage of the stereotypic response which results from the sensitization reaction, without affecting the quantitative portion of the response attributable to the acute effect of amphetamine.

Delta-9-tetrahydrocannabinol depresses inward sodium current in mouse neuroblastoma cells.

Whole-cell voltage-clamp techniques were used in order to define the effects of delta-9-tetrahydrocannabinol (THC) on the voltage-gated sodium current in neuroblastoma cells. With regard to the inward sodium current, THC decreased the peak amplitude and increased both the time to peak and tau for recovery. The reversal potential was unchanged, suggesting that channel selectivity for sodium was not altered by the drug.