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Biomedical subjects

M D Schechter

Publications and source records attributed to M D Schechter.

192 records · Page 11Linked to original sources
PubMedDate not supplied

Can ACTH analogs support discriminative learning in rats?

Ten rats were trained to discriminate between the stimulus properties of subcutaneously (SC) administered MSH/ACTH4-10 and saline in a two-lever, food-motivated operant task. After 12 weeks of discriminative training with 100 micrograms/kg MSH/ACTH4-10, half the rats received 200 micrograms/kg MSH/ATCH4-10, whereas the other half were administered 400 micrograms/kg, for 6 additional weeks. Subsequently, all rats continued training on 50 micrograms/kg ORG 2766 (SC) and, after 12 weeks of training, were randomly assigned to receive either 100 or 200 micrograms/kg ORG 2766. The results of this extensive 36 week training schedule indicate that only 1 of the 10 rats learned to discriminate the interoceptive cues produced by the ACTH analogs. However, this rat's performance was so sustained and errorless that the possibility exists that it was relatively more sensitive to the effects of MSH/ACTH4-10 and its analogs and that these substances may support discriminative learning in the rat.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Interaction of ethanol and tetrahydro-beta-carboline (THBC) in a discriminative task.

Rats (n = 10) were trained to discriminate between ethanol (600 mg/kg, IP) and its vehicle, or between THBC (20 mg/kg) and its vehicle in a two-lever food-motivated operant task. Once the discriminative training criterion was attained, rats in each group were administered different doses of both ethanol and THBC. The ED50 of ethanol in the ethanol-trained rats was 298.0 mg/kg and 15 mg/kg THBC produced ethanol-like responding. The ED50 of THBC in the THBC-trained rats was 3.63 mg/kg and 1200 mg/kg ethanol produced THBC-like responding. The cross-generalization between ethanol and THBC is, thus, indicated and relates to previous evidence in which both ethanol- and THBC-trained rats generalize to a common agent, TFMPP, a putatively specific 5HT1B receptor agonist. Taken together, these observations suggest that beta-carbolines may play a role in the discriminative stimulus properties of ethanol.

Animals↗
PubMedDate not supplied

Time-dependent effect of ethanol upon discrimination behavior.

The discriminative stimulus properties produced by ethanol were employed to demonstrate differences in discriminative performance over time in rats trained at different postinjection times. Thus, one group of rats was trained to discriminate between intraperitoneally administered 600 mg/kg ethanol and its distilled water vehicle at 6-min postadministration, whereas a second group of rats was trained to make this discrimination when trained at 30-min postinjection. Subsequent to reaching criterion performance, dose-response relations to doses of ethanol from 150-900 mg/kg were determined to be similar in both groups. This indicated that the discriminative stimulus effects at the two postadministration times were equally effective for training of behavioral responding to ethanol. The rats trained at 30 min postadministration maintained criterion level discrimination performance when tested at 6-, 15- and 60-min postinjection. In contrast, the rats trained at 6-min postadministration discriminated ethanol at a reduced level (40%) when tested at 30-min postinjection. These results suggest that the nature of the discriminable stimuli produced by a low dose of ethanol are different at 6-min and at 30-min postadministration. Evidence is cited to further suggest that the earlier stimuli are excitatory whereas the later stimuli are sedative.

Animals↗
PubMedDate not supplied

HAD and LAD rats respond differently to stimulating effect but not discriminative effects of ethanol.

The drug discrimination paradigm (DD) was used to evaluate behavioral differences of rats selectively bred for differential ethanol drinking preferences. Seventh-generation high alcohol-drinking (HAD) and low alcohol-drinking (LAD) rats were trained to discriminate between ethanol (0.5 g/kg, IP) and saline vehicle, following a 2-min presession interval (PI), using an FR-10 schedule of reinforcement. The HAD line was more responsive than the LAD line to the stimulating effect of ethanol as measured by total response rates. ED50 values of 0.239 and 0.244 g/kg for the HAD and LAD lines, respectively, do not reflect any difference in the discriminative effects of ethanol. Response rates during DD indicated a dissociation of rate-increasing effects and discriminative performance following ethanol. In addition to differential drinking preference, these data suggest that selective breeding for the HAD and LAD animals also involves the stimulant action of ethanol but not on the discriminative effects.

Alcohol Drinking↗
PubMedDate not supplied

Ethanol-produced interoceptive stimuli are time dependent in selectively bred HAS and LAS rats.

Fourteenth generation high alcohol-sensitive (HAS) and low alcohol-sensitive (LAS) rats were trained to discriminate the effects of 600 mg/kg intraperitoneally administered ethanol from its vehicle at 6 and 30 min postadministration. Each of the earlier- and later-trained animals were given lower doses of ethanol and ED50 values at their trained postadministration interval were found to be nonsignificantly different. Thus, there was no difference between HAS and LAS animals as to their sensitivity to the discriminative effects of ethanol. Phase-generalization studies, where rats trained at 6 min postadministration were tested with the drug at 30 min postadministration were shown not to generalize, whereas the animals trained at 30 min postadministration and tested at 6 min postinjection were shown to readily discriminate the discriminative stimuli. This asymmetrical generalization lends evidence to the biphasic action of ethanol, and suggests that the earlier phase is quantitatively different than the latter phase. The similarity in sensitivity of the LAS and HAS animals, furthermore, suggests that the discrimination of ethanol is not based on its hypnotic effects.

Animals↗
PubMedDate not supplied

Locomotor activity but not conditioned place preference is differentially affected by a moderate dose of ethanol administered to P and NP rats.

The conditioned place preference (CPP) test and spontaneous motor activity were used in order to determine if ethanol-preferring (P) rats differ from ethanol nonpreferring (NP) rats after the administration of a moderate (1.0 g/kg) dose of ethanol. Results indicate that both of the selectively bred lines of rats found ethanol aversive, with little difference between the P and the NP rats. In contrast, the NP rats were shown to be more sensitive to the motor-impairing effect of ethanol.

Alcohol Drinking↗
PubMedDate not supplied

The NMDA receptor antagonist MK-801 produces ethanol-like discrimination in the rat.

Two groups of rats, one derived from N/Nih stock and the second from the (putatively) serotonin-compromised Fawn-Hooded line, were trained to discriminate ethanol from its vehicle in a drug discrimination paradigm. Once each of the two groups attained discrimination criterion, dose-response relationships with lower doses of ethanol indicated that the Fawn-Hooded rats were less sensitive (ED50 value = 579.5 mg/kg) than the N/Nih rats (ED50 = 371.4 mg/kg). Testing of various doses of the NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 produced complete generalization in each group of animals, with a similar difference in ED50 values between N/Nih and Fawn-Hooded lines. These results extend previous ethanol-to-MK-801 generalization reported in pigeon, and are discussed in light of a possible NMDA-mediated contribution to the ethanol-induced discriminative stimulus cues.

Animals↗
PubMedDate not supplied

Ethanol discrimination in Fawn-Hooded rats is compromised when compared to other strains.

The drug discrimination paradigm was used to evaluate the behavioral differences in response to ethanol between three strains of rats, viz., Sprague-Dawley, N/Nih and Fawn-Hooded. This latter group is thought to have a genetically-transmitted diminished central serotonin function. Each group of rats was trained to discriminate between the stimulus properties of 600 mg/kg ethanol and its vehicle in a two-lever, food-motivated operant task. Results indicate that the Fawn-Hooded rats required a significantly longer time and a higher ethanol dose to reach criterion discrimination performance. Furthermore, the ED50 value of the Fawn-Hooded rats, once trained, was higher than the Sprague-Dawley or N/Nih rats. The possibility that a reciprocal relationship exists between lowered central serotonin concentrations and higher alcohol consumption is suggested and the hypothesis that the diminished ability to recognize the interoceptive stimuli produced by ethanol may result in larger amounts of ethanol being consumed is offered.

Animals↗
PubMedDate not supplied

Cocaethylene-induced lethality in mice is potentiated by alcohol.

Mice of the heterogeneously bred HS line were concurrently administered intraperitoneal injections of either 95, 75, 60, or 48 mg/kg cocaethylene or 48, 38, or 30 mg/kg cocaethylene in conjunction with the non-lethal dose of 6.0 g/kg (20% w/v) alcohol. Results indicate that alcohol administration significantly potentiated cocaethylene-induced lethality. This observation suggests that alcohol is capable of enhancing the lethal effects of cocaethylene. Results are discussed in terms of observations of sudden death in humans who abuse cocaine and alcohol.

Animals↗
PubMedDate not supplied

MDMA (Ecstasy) substitutes for the ethanol discriminative cue in HAD but not LAD rats.

Selectively bred high- and low-alcohol-drinking (HAD/LAD) rats were trained to discriminate the interoceptive stimuli produced by IP-administered 600 mg/kg ethanol (10% w/v in a two-lever, food-motivated operant task. Once criterion discrimination was attained, animals were tested with 3.0, 1.5, 1.0, and 0.5 mg/kg MDMA. Although no differences in alcohol discrimination were observed between the HAD and LAD animals, the HAD line was significantly more sensitive than the LAD line to the effects of MDMA. These results provide additional information to the growing body of evidence suggesting serotonergic mediation of some of the behavioral effects of ethanol.

Alcohol Drinking↗
PubMedDate not supplied

Discriminative stimulus effect of phenylephrine.

Rats were trained to discriminate phenylephrine in a two-lever, food-motivated operant task by increasing the i.p. administered training dose from 0.8 to 2 mg/kg. Stable discrimination to 2 mg/kg phenylephrine was established and testing of 0.5-2.5 mg/kg was shown to be dose-responsive and allowed for a calculated ED50 value of 0.87 mg/kg. Administration of methoxamine (0.5-6 mg/kg), another alpha 1-adrenoceptor agonist, produced a dose-responsive generalization, whereas only the lowest (0.04 mg/kg) and highest (0.12 mg/kg) doses of the alpha 2-adrenoceptor agonist clonidine produced generalization in the phenylephrine-trained rats. Likewise, yohimbine (2.5-4.5 mg/kg) generalized, whereas pretreatment with prazosin (0.1-0.4 mg/kg), the alpha 1-adrenoceptor antagonist, dose-responsively decreased phenylephrine discrimination. The results would indicate that phenylephrine is capable of controlling differential responding in a drug discrimination paradigm and would suggest that this effect is centrally mediated. The possibility that peripheral administration of phenylephrine (Neosynephrine) affects the brain in chronic users of nasal decongestants is discussed.

Adrenergic alpha-Agonists↗