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Biomedical subjects

M D Schechter

Publications and source records attributed to M D Schechter.

At least 109 records · Page 6Linked to original sources
PubMed1986

Dopaminergic mediation of a behavioral effect of l-cathinone.

Ten male rats were trained to discriminate between the stimulus properties of 0.6 mg/kg l-cathinone and saline in a two-lever food-motivated operant task. Once trained, rats showed a dose-dependent increase in discrimination over a dosage range of 0.15-1.2 mg/kg l-cathinone. Analysis of this dose-response relationship indicated an ED50 of 0.27 mg/kg. Pretreatment with 0.2 mg/kg of the specific dopamine blocking drug haloperidol increased this ED50 to 0.47 mg/kg and significantly decreased discriminative performance when co-administered with either 0.15, 0.3, or 0.6 mg/kg l-cathinone. Since the dose-effect curves for cathinone with and without haloperidol pre-treatment were parallel, it is suggested that l-cathinone, the active constituent in khat, produces its discriminative properties, in part, by mediation of dopaminergic neuronal systems.

Alkaloids↗
PubMed1986

Discriminative properties of l-cathinone compared to dl- and d-cathinone.

Rats were trained to discriminate between the stimulus properties of 0.6 mg/kg l-cathinone and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-dependent decrease in discrimination performance with lower l-cathinone doses and analysis of the dose-response relationship indicated an ED50 of 0.19 mg/kg. Administration of either dl-or d-cathinone produced a pattern of discriminative responding similar to l-cathinone with ED50s of 0.29 and 0.63 mg/kg, respectively. Thus, the potency of the racemeric cathinone lies approximately midway between that of the two isomers. Time-course data indicate that l-cathinone has a peak effect at 15-30 min post-administration with a duration of 180 min. Pretreatment with the serotonic receptor blocker pirenperone did not affect l-cathinone discrimination, whereas pretreatment with 0.2 mg/kg haloperidol, a dopamine receptor blocking agent, attenuated the l-cathinone discrimination. These data suggest that the stimulus properties of l-cathinone are possibly mediated by brain dopaminergic systems.

Alkaloids↗
PubMed1986

Serotonergic mediation of tetrahydro-beta-carboline.

Rats were trained to discriminate between the stimulus properties of tetrahydro-beta-carboline (THBC) and its vehicle in a two-lever, food-motivated operant task. By steadily increasing the training dose, the discrimination was attained at 20.0 mg/kg THBC. Dose-response experiments subsequently indicated that decreasing doses of THBC produced decreased discrimination and generated an ED50 = 3.63 mg/kg. Administration of the serotonergically-active drug, fenfluramine, produced THBC-appropriate responding in a dose-responsive manner. In addition, LSD and yohimbine produced partial generalizations in the THBC-trained rats. These data suggest that the discriminative stimulus properties of THBC are mediated by serotonergic neurons in the central nervous system.

Animals↗
PubMed1986

Induction of and recovery from tolerance to the discriminative stimulus properties of l-cathinone.

Rats previously trained to discriminate between 0.6 mg/kg l-cathinone and saline in a two-lever, food-motivated operant task were administered l-cathinone at the same dose, every 8 hours for 10 days. Discrimination testing during this chronic administration phase of experimentation indicated that the animals' ability to discriminate both 0.3 and 0.6 mg/kg l-cathinone decreased when compared to their discriminative ability prior to chronic administration. In contrast, discrimination of the non-drug state, i.e., saline, was not affected. Comparison of dose-response curves prior to and during chronic cathinone administration indicated a 3-4 fold shift to the right for the latter curve. Continued testing after termination of chronic treatment resulted in a return to pre-chronic discriminative performance by the fifteenth day after cessation. These results indicate that tolerance to the discriminative effects of l-cathinone can be produced within 10 days of chronic administration and recovery from this observed tolerance occurs within 15 days of cessation of chronic administration.

Alkaloids↗
PubMed1986

Discriminative profile of MDMA.

Groups of rats were trained to discriminate the stimulus properties of dopaminergically and/or serotonergically active drugs, viz., apomorphine, fenfluramine, tetrahydro-beta-carboline (THBC) and l-cathinone. Once trained, these animals were given several doses of drugs used in training and dose-response relationships and ED50 values were generated. Subsequently, each group of trained rats was administered various doses of 3,4-methylenedioxymethamphetamine (MDMA) to test generalization of the interoceptive cue of the drug used for training to MDMA. Rats trained to fenfluramine, THBC, and l-cathinone were observed to discriminate MDMA in a manner similar to the drug state to which they had been trained. Analysis of dose-response curves suggested that MDMA may be acting both as an indirect dopaminergic agonist and as a serotonergic receptor agonist. This duality of effect of MDMA has been evidenced by other studies and may account for its present abuse potential.

3,4-Methylenedioxyamphetamine↗
PubMed1986

Nicotine-induced potentiation of ethanol discrimination.

Rats were trained in a 2-lever, food-motivated operant task to discriminate intraperitoneal administration of ethanol (600 mg/kg) from vehicle. Dose-response curves for the ethanol cue were analyzed before and after pre-treatment of rats with intraperitoneal doses of 0.4 mg/kg or 0.2 mg/kg nicotine. Results demonstrate that nicotine potentiates ethanol-appropriate responding in test sessions. The results are discussed in light of the recognized correlation between smoking and alcohol intake.

Animals↗
PubMed1985

Ethanol-chlordiazepoxide interactions in the rat.

One group of rats (n = 9) was trained to discriminate between the effects induced by 600 mg/kg ethanol and saline, whereas another group (n = 5) had to discriminate between 5.0 mg/kg chlordiazepoxide (CDZ) and saline, administered intraperitoneally (IP) 15 min prior to the training sessions. Once trained, decreasing doses of ethanol in ethanol-trained rats produced decreased discriminative performance; the ED50 was 239.4 mg/kg. Likewise, decreasing doses of CDZ in CDZ-trained rats produced decreased discrimination, with an ED50 = 1.5 mg/kg. Substitution of 1.25-10.0 mg/kg CDZ in ethanol-trained rats produced a transfer of the ethanol-induced interoceptive cue in a dose-responsive manner, whereas ethanol did not substitute for CDZ in CDZ-trained rats. Analysis of dose-response curves suggested that CDZ is acting by a similar mechanism/site in both groups of rats but by a site different than ethanol. Co-administration of the ED50's for ethanol and CDZ in ethanol-trained rats did not produce additive effects. The observed one-way asymmetrical generalization of drug effects, as well as the lack of additive effects of co-administration, are discussed.

Animals↗
PubMed1985

Effect of dopamine agonists and fenfluramine on discriminative behavior in obese and lean Zucker rats.

Dopamine agonists and fenfluramine were used as pharmacological probes to investigate the possible difference in sensitivity and time course of drug action in genetically obese Zucker rats and their lean littermates. All rats were trained to discriminate between the stimulus properties of 0.6 mg/kg d-amphetamine and its vehicle in a two-lever, food-motivated operant task. Once trained, both groups of rats showed a dose-related decrease in discriminative performance with lower amphetamine doses. Analysis of the dose-response curves indicated an ED50 for the obese rats of 0.17 mg/kg and for the lean group of 0.14 mg/kg. Administration of 0.3-1.2 mg/kg l-amphetamine and 2.5-10.0 mg/kg cocaine produced a pattern of responding similar to that observed with d-amphetamine. In contrast, 0.08-mg/kg apomorphine produced saline-appropriate responding and 1.5-2.5 mg/kg fenfluramine produced intermediate results in both groups. Time-course experiments indicated that the lean rats maintain errorless discriminative performance through 90 min post-injection, whereas the obese rats discriminate d-amphetamine significantly less at that post-administration time. The results suggest a similar sensitivity to d-amphetamine and other dopaminergic agonists in obese and lean rats with a difference in the time-course of d-amphetamine's action between these two groups.

Amphetamine↗
PubMed1985

Cathinone, cocaine and methamphetamine: similarity of behavioral effects.

The discriminative stimulus properties of (+/-)-cathinone were tested by training eight rats to discriminate between the interoceptive cues produced by 0.6 mg/kg (+/-)-cathinone and saline in a food-reinforced, two lever operant task. Doses of cocaine and methamphetamine were observed to transfer to the cathinone cue and all three drugs exhibited decreased discriminative performance with decreasing doses. The ED50 for (+/-)-cathinone, (+/-)-methamphetamine and cocaine were 0.23, 0.17, and 1.97 mg/kg, respectively, and the three curves were shown to be parallel. These data indicate the possibility of a common mechanism/site of action for these three stimulants, presumably by their actions upon central dopaminergic neurons.

Alkaloids↗
PubMed1985

Apomorphine increases ethanol discrimination.

Rats were trained to discriminate between the stimulus properties of 600 mg/kg ethanol and saline in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance with lower ethanol doses and analysis of the dose-response curve indicated an ED50 of 372 mg/kg. Pretreatment with 0.16 mg/kg apomorphine produced increased discriminative performance at each ethanol dose and the combination generated a dose-response curve parallel to ethanol administered alone with an ED50 of 232 mg/kg. This significant shift to the left of the ethanol dose-response curve after apomorphine administration is discussed in relation to dopaminergic neuronal systems and the clinical use of apomorphine alcoholics.

Animals↗
PubMed1985

Behavioral and neurochemical effects of (-)- and (+/-)-cathinone: dose-response and time-course.

The purpose of the present study was to compare (-)-cathinone and its analogue (+/-)-cathinone using behavioral and neurochemical measures. Rats were trained to discriminate between 0.6 mg/kg (-)- or (+/-)-cathinone and saline in a food-motivated, two-lever operant task. In addition, concentrations of dopamine, norepinephrine, 5-hydroxytryptamine and their major metabolites were analyzed in the nuclei accumbens and septi lateralis. The results suggest that (-)- and (+/-)-cathinone have similar effects on behavior and neurochemistry with (-)-cathinone being more potent.

Alkaloids↗
PubMed1984

Differential effects of apomorphine in 6-hydroxydopamine-treated and aged rats.

Effects of dopamine depletion and old age were tested on the ability of rats to discriminate the interoceptive cue produced by IP administered apomorphine. In Experiment 1, rats were administered IC injections of 6-hydroxydopamine or its vehicle at 5 days of age. Administration of this dopamine neurotoxin resulted in significant depletion of whole-brain dopamine to 27.2% of controls as indicated when the brains of littermate rats, killed at 35 days of age, were analyzed by high-pressure liquid chromatography. Although this dopamine depletion was significant, toxin-treated rats learned to discriminate 0.16 mg/kg apomorphine from saline at the same rate as control rats. However, the dose-response curve for apomorphine discrimination after doses of 0.04-0.24 mg/kg suggested hypersensitivity to the dopamine agonist in toxin-treated rats. In Experiment 2, senescent rats were similarly trained to discriminate apomorphine in the two-lever food-motivated operant task. Dose-response testing indicated hypersensitivity similar to that found in 6-OHDA-treated rats. This increased behavioral responsiveness of aged rats to dopamine agonists is discussed in relation to receptor supersensitivity, metabolic rates, and blood-brain barrier permeability.

Aging↗
PubMed1984

Discriminative stimulus properties of S(-)- and R(+)-cathinone, (+)-cathine and several structural modifications.

Rats trained to discriminate between the stimulus properties of 0.6 mg/kg of racemic cathinone and its vehicle, in a two-lever operant task for food reinforcement, were administered doses of S(-)-cathinone, R(+)-cathinone, (+)-cathine and several structurally-related derivatives, in order to study structure-activity relationships. The optical isomers of cathinone and (+)-cathine produced patterns of responding similar to that observed with the training drug; S(-)-cathinone (ED50 = 0.22 mg/kg) was the more active of the two isomers, while R(+)-cathinone (ED50 = 0.72 mg/kg) was more active than (+)-cathine (ED50 = 1.61 mg/kg). In contrast, removal of the alpha-methyl group of cathinone, or substitution at the 4-position of racemic cathinone by a hydroxyl, methoxyl or chloro group, essentially abolished activity at dose levels comparable to the training dose of cathinone.

Alkaloids↗
PubMed1984

Evidence for a direct dopaminergic effect of lisuride.

The discriminative stimulus properties of the clinically important ergot derivative lisuride hydrogen maleate were studied by training 2 groups of rats to discriminate 0.04 mg/kg lisuride from saline and 0.16 mg/kg apomorphine from saline. Dose-response and substitution tests between these groups showed that lisuride and apomorphine are discriminated similarly by both groups and that lisuride is 5 to 9 times more potent. The dopaminergic agonists d-amphetamine, quipazine, bromocriptine, cocaine and cathinone did not substitute for lisuride. In antagonism studies, only the dopamine receptor blocker haloperidol attenuated the lisuride cue; the serotonin receptor blockers pirenperone and BC-105 were ineffective. These data indicate that the primary central action mediating the discriminative stimulus effects of lisuride was direct activation of dopamine receptors.

Animals↗
PubMed1984

Comparison of behavioral effects of cathinone, amphetamine and apomorphine.

Rats were trained to discriminate between the stimulus properties of 0.6 mg/kg +/- -cathinone and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance with lower cathinone doses and analysis of the dose-response curve indicated an ED50 of 0.24 mg/kg. Administration of 0.2-0.8 mg/kg d-amphetamine produced a pattern of responding similar to that observed with cathinone. The dose-response curve after d-amphetamine was shown to be parallel to that of cathinone and the ED50 generated was 0.21 mg/kg. Thus, cathinone was equi-potent to d-amphetamine in this behavioral paradigm. In contrast, administration of 0.16-0.32 mg/kg apomorphine produced intermediate results. The results suggest a common site and/or mechanism for action of +/- -cathinone and d-amphetamine.

Alkaloids↗
PubMed1984

Ethanol and pentobarbital have different behavioral effects in the rat.

Stimulus control was established in rats with 600 mg/kg ethanol and saline by employing a two-lever response choice task and an FR10 schedule of food reinforcement. Once trained, rats were tested with lower doses of ethanol (300 and 450 mg/kg) and with pentobarbital (0.75 - 4.0 mg/kg). The 3.0 and 4.0 mg/kg doses of pentobarbital were observed to produce ethanol-like responding and decreasing doses of both ethanol and pentobarbital produced dose-related effects upon discriminative performance. The ED50 for ethanol was 372 mg/kg and for pentobarbital was 1.09 mg/kg. Graphic representation of the dose-response relationships suggested that these drugs possess different sites and/or mechanisms of action.

Animals↗
PubMed1984

Specific antagonism of the behavioral effects of chlordiazepoxide and pentobarbital in the rat.

Stimulus control was established in rats with 5 mg/kg chlordiazepoxide and saline by employing a two-lever response choice task and an FR10 schedule of food reinforcement. Once trained, administration of chlordiazepoxide doses different from the training dose produced dose-responsive discrimination responding and the chlordiazepoxide discriminative cue was observed to transfer to pentobarbital. Pretreatment with the convulsant bemegride antagonized the pentobarbital transfer but not the chlordiazepoxide cue, whereas the specific benzodiazepine antagonist RO15-1788 decreased the chlordiazepoxide cue in a dose-response manner without attenuating the pentobarbital transfer. Results confirm and expand upon other recent studies that suggest different mechanisms of action for chlordiazepoxide and pentobarbital.

Animals↗