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Biomedical subjects

B T Ho

Publications and source records attributed to B T Ho.

At least 73 records · Page 4Linked to original sources

Metabolism correlates of cocaine-induced stereotypy in rats.

An increase in stereotyped behavior was observed in rats injected daily with cocaine (40 mg/kg, IP), as compared with the first day. This increase persisted 14 days after discontinuation of the drug treatment, and corresponded to increased levels of 3H-cocaine norcocaine and benzoylecgonine in brain. Pretreatment of the animals with SKF-522A, an inhibitor of cocaine demethylation, produced a decrease in stereotypy rating and concomitantly a lower level of 3H-norcocaine in the brain. The role of this metabolite in the production of cocaine-induced stereotyped behavior is discussed.

Animals↗

Generalization of norcocaine to the discriminative stimulus properties of cocaine.

In rats trained to discriminate 10 mg/kg cocaine from 1 mg/kg saline, norcocaine, the N-demethylated metabolite, at doses of 2.5 mg/kg, 5 mg/kg and 10 mg/kg, produced a dose response curve similar to that of cocaine and generalized to cocaine at the two higher doses. As with cocaine, the discriminative stimulus produced by the norcocaine was partially attenuated by the dopaminergic antagonist pimozide and the amine depletor reserpine. Benzoylecgonine, benzoylnorecgonine and ecgonine methyl ester in doses of 10 mg/kg and 20 mg/kg did not generalize to cocaine.

Animals↗

The uptake of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline and its effect on 5-hydroxytryptamine uptake and release in blood platelets.

The uptake of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeOTHBC, 5-methoxytryptoline) by rabbit blood platelets was studied by using 3H-labelled compound. A high rate active uptake (Km 6.6 micron), which was inhibited by 5-hydroxytryptamine (5-HT) and cinnanserine, and a slow rate uptake, not inhibited by 5-HT were observed. The intracellular distribution of 3H-6-MeOTHBC in platelets clearly differed from that of 14C-5-HT. 6-MeOTHBC also competitively inhibited the high-rate active (but not the slow passive) uptake of 14C-5-HT, being more active than 5-HT itself. The spontaneous release of the newly taken-up 14C-5-HT from platelets was increased only with high concentrations of 6-MeOTHBC.

Animals↗

Major pharmacological effects of 6-methoxytetrahydro-beta-carboline, a drug elevating the tissue 5-hydroxytryptamine level.

Major pharmacological effects of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-methoxytryptoline, 6-MeOTHBC) are described. It seemed to have a weak effect of its own on 5-HT-receptors. It is concluded that most of the effects, like the increase of rectal temperature after peripheral administration and decrease and then increase after intrahypothalamic application as well as the antagonism of the group toxicity of amphetamine without effect on norepinephrine toxicity or barbiturate sleeping time, can result from the increase of tissue 5-HT-concentration and/or inhibition of 5-HT-uptake.

Acute Disease↗

Comparison of inhibition of monoamine uptake by cocaine, methylphenidate and amphetamine.

Amphetamine and methylphenidate both inhibited the uptake of 3H-norepinephrine (NE) and 3H-dopamine (DA) although the activity (as measured by I50 and Ki values) of d-amphetamine was lower with respect to uptake of the two catecholamines in synaptosomes from thalamus-hypothalamus and and striatum. Cocaine was a much stonger inhibitor of 3H-5-hydroxytryptamine (5-HT) uptake in septum-caudate synaptosomes than amphetamine or methylphenidate. The I50 values were 70, 118 and 570 micron for cocaine, methylphenidate and d-amphetamine, respectively. The results of the present study suggested that a serotonergic system may be involved in the stimulant properties of cocaine. It may also explain certain differences in pharmacological activities between cocaine and the other two stimulants as described in the literature.

Animals↗

Neurochemical effects of cocaine following acute and repeated injection.

Following repeated injection in the rat, cocaine decreased the concentration of serotonin in the septum-caudate and increased the metabolism of hypothalamic norepinephrine and also striatal dopamine to a lesser extent. Furthermore, cocaine significantly decreased the activity of the rate-limiting enzyme, tryptophan hydroxylase. In a comparative study d-amphetamine and methylphenidate were found to exert an effect opposite to cocaine in the activation of tryptophan hydroxylase. These findings indicate that cocaine may lower central serotonin function by decreasing its availability for neural transmission. This could account for the stimulation of locomotor activity observed after cocaine administration.

Animals↗

Induced tolerance to the discriminative stimulus properties of cocaine.

Twenty-five male Sprague-Dawley rats were trained in five two-lever operant chambers on a DRL-15 sec schedule of positive food reinforcement to discriminate 10 mg/kg cocaine from 1 ml/kg saline. Following acquistions of discrimination a counterbalanced design of extinction tests was performed before and after repeated administration of 20 mg/kg cocaine or saline (three times a day at five hr intervals for seven days). The extinction tests consisted of testing responses of animals following 1 ml/kg saline, 2.5 mg/kg cocaine, or 5 mg/kg cocaine. The results showed no significant difference in animals' level choice before and after repeated injection with saline. However, the percent cocaine lever choice with the two doses of cocaine was lower after repeated administration of cocaine than before the repeated injections. This indicates tolerance developed to the discriminative stimulus properties of cocaine.

Animals↗

Inhibition of the metabolism of cocaine by SKF-525A.

In vitro and in vivo studies in rats indicate cocaine to be metabolized primarily in the liver to form benzoylecgonine and norcocaine. The formation of these metabolites was significantly hindered by SKF-525A, a microsomal enzyme inhibitor. In in vivo studies, pretreatment of rats with SKF-525A prior to receiving cocaine resulted in increased amounts of unchanged cocaine in the brain. No accompanying increase in spontaneous motor activity was observed for these animals, indicating a possible role for metabolites in the stimulant action of cocaine.

Animals↗

Effect of delta-THC on ethanol withdrawal in mice.

Delta-THC (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when delta-THC was administered chronically during the exposure to ethanol.

Alcoholism↗