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A C Collins

Publications and source records attributed to A C Collins.

At least 199 records · Page 11Linked to original sources

Activating and anesthetic effects of general depressants.

The long-sleep (LS) and short-sleep (SS) lines of mice were derived by selective breeding with respect to ethanol sleep time. We found that in current generations LS mice also have longer sleep times than SS mice to trichloroethanol and paraldehyde. Two subsequent experiments tested our hypothesis that mice that are relatively insensitive to the hypnotic effects of depressant drugs might be relatively activated by low doses of these drugs. Both experiments failed to support the hypothesis. First, although SS mice were more activated than LS mice by subhypnotic doses of paraldehyde, the lines did not differ in the degree of activation produced by low doses of trichloroethanol. Second, among mice from a genetically heterogeneous population (HS), there was no relation between the degree of activation induced by a low dose of ethanol and sensitivity to the hypnotic effects of a higher dose.

Animals↗

Effects of three monoamine oxidase inhibitors on ethanol preference in mice.

These experiments investigated the effects of pargyline, N-[2-(o-Chlorophenoxy)-ethyl]-cyclopropylamine (Lilly 51641), and nialamide on voluntary ethanol consumption of C57BL/6J mice. Both pargyline and Lilly 51641 reduced ethanol preference; in contrast, nialamide did not affect preference, despite the fact that it inhibited MAO activity by more than 90%. A subsequent experiment determined that both pargyline and Lilly 51641 produced substantially greater elevations in acetaldehyde levels than did nialamide. It is suggested that increased acetaldehyde is the mechanism responsible for the reduction in ethanol preference observed with pargyline and Lilly 51641.

Acetaldehyde↗

Influences of genotype and sex on behavioral tolerance to nicotine in mice.

Spontaneous motor activity in a Y-maze was measured in DBA/2Ibg and C57BL/6Ibg mice which had received nicotine or saline injections three times a day for two, four or seven days. Both genotype and sex influenced the development of tolerance to nocotine's effects on spontaneous motor activity, with DBA males requiring the longest exposure to nicotine and C57 males requiring the shortest drug exposure for tolerance development. DBA and C57 females developed behavioral tolerance equally after two days of pretreatment, but the C57 females showed a greater degree of tolerance after seven days of injections than did the DBA females. The development of behavioral tolerance in DBA males after four days of nicotine pretreatment was associated with the development of behavioral tolerance in DBA males after four days of nicotine pretreatment was associated with the development of drug dispositional tolerance, with minimal evidence for a change in nervous system sensitivity. Drug dispositional tolerance in DBA females, C57 males and C57 females, however, did not seem to affect spontaneous motor activity.

Animals↗

Role of liver cytosolic aldehyde dehydrogenase isozymes in control of blood acetaldehyde concentrations.

The role of various cytosolic aldehyde dehydrogenase (ALDH) isozymes in acetaldehyde metabolism was determined. Rats of known genotype (RR, reactor; rr, nonreactor) with respect to induction of a cytosolic enzyme by phenobarbital were used. Animals were treated with either phenobarbital (1.0 mg/ml in drinking water for 3 days) or 75 microng/kg (i.p.) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prior to ethanol treatment (2.5 g/kg). TCDD treatment is known to induce a second cytosolic ALDH isozyme in both RR and rr animals. Phenobarbital increased cytosolic ALDH activity 23-fold only in the RR animals, while TCDD increased activity 155-fold in both groups. Phenobarbital-treated RR rats maintained significantly lower blood acetaldehyde levels at 30, 90 and 150 minutes after ethanol injection compared to control RR animals. Blood acetaldehyde levels in phenobarbital-treated rr rats were not significantly different from rr controls. Administration of TCDD to RR or rr rats did not significantly alter blood acetaldehyde levels at 30, 90 or 150 minutes after ethanol treatment compared to appropriate controls. Similarly, phenobarbital significantly increased blood ethanol elimination rate (1.5 times greater than control) only in RR rats. Ethanol elimination rate was not significantly altered by TCDD in either group. Pargyline (100 mg/kg i.p.) did not significantly inhibit cytosolic ALDH activity, while total mitochondrial ALDH activity was inhibited by 28 and 57% in RR animals receiving TCDD and phenobarbital, respectively. Pargyline significantly increased blood acetaldehyde levels after ethanol administration. However, pretreatment with phenobarbital or TCDD significantly decreased elevated blood acetaldehyde levels resulting from pargyline treatment, with the greatest reduction in the phenobarbital-treated RR animals.

Acetaldehyde↗

Reduction of alcohol selection by pargyline in mice.

Drugs which increase brain levels of serotonin (5-HT) have frequently been found to cause a decrease in voluntary ethanol consumption. Results obtained with parachlorophenylalanine (pCPA), which decreases 5-HT, have been less consistent. The present investigation compared the effects of pCPA on alcohol selection with those of pargyline, a monoamine oxidase inhibitor which increases brain levels of 5-HT. Ingestion of a 10% ethanol solution was assessed in male C57BL/6J mice given daily injections of 250 or 300 mg/kg pCPA, 50 mg/kg pargyline, or saline. An additional control group received no treatment. A two-bottle preference procedure was employed, and ethanol and water intake were recorded during a pretreatment period (11 days), a treatment period (8 days), and a posttreatment period (10 days). Like other agents which increase 5-HT, parygyline produced a depression in ethanol intake which lasted beyond the time of drug administration. pCPa had no effect on ethanol ingestion either during the period of drug administration or afterwards.

Alcohol Drinking↗

Methaqualone: tolerance and physical dependence in mice.

Tolerance and physical dependence was produced in C57Bl/6 male mice that had been exposed, for 36 days, to methaqualone in food pellets via an automated system. Tolerance was revealed in the reduction of sleep-times following intraperitoneal injection of methaqualone. Physical dependence was manifested as an alteration in neural sensitivity to flurothyl-induced convulsions.

Animals↗

Mast cell histamine and ovarian follicular growth in the lizard Anolis carolinensis.

The hypothesis is proposed that histamine released from mast cells in the theca of ovarian follicles increases thecal hyperemia and vessel permeability, and thus plays a role in follicular growth in Anolis carolinensis. Mast cells are present in the stroma and theca, and the number of thecal mast cells increases as follicles grow. The levels of histamine in follicular walls varies with follicular size. Histamine causes vasodilatation of thecal vessels. Antihistamine blocks the effects of histamine and, when given alone, stimulates vasoconstriction. Antihistamine also blocks estradiol-induced growth of large follicles. These findings are consistent with the above hypothesis.

Animals↗

Variations in alcohol metabolism: influence of sex and age.

Alcohol-induced sleep time was measured subsequent to the intraperitoneal injection of a 3.5 g x kg-1 dose. The old male group had a sleep time approximately 4 times that of the young male group and approximately twice that of the old female group. Blood alcohol concentrations at time of awakening were nearly identical in all groups, indicating the difference in sleep time is not due to an altered CNS sensitivity. Measurement of in vivo alcohol disappearance rate indicates the old male group is different from the other groups because of a slower rate of alcohol metabolism. Although changes in hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were seen, the changes do not explain the observed decrease in alcohol metabolism observed in the old male group. These data provide further evidence that hepatic ADH and ALDH activities are not rate limiting in alcohol metabolism.

Age Factors↗

Ethanol and acetaldehyde metabolism in the pregnant mouse.

Liver aldehyde dehydrogenase (ALDH) activity was found to be two-fold greater in pregnant (days 16-20 of gestation) mice than in non-pregnant controls. A subcellular fractionation revealed that the increase in ALDH activity was confined to the cystosolic fraction of the liver. Kinetic characterization of partially purified liver ALDH revealed similar Km values for either acetaldehyde or propionaldehyde in pregnant and non-pregnant animals. The similarity of apparent Km values suggests that the increase in cytosolic ALDH may involve induction of normally present ALDH isozyme, rather than originating from synthesis of a new enzyme. Induction of liver ALDH was found to significantly decrease blood acetaldehyde concentrations in pregnant mice receiving 2.0 or 3.0 g/kg ethanol when compared to the respective control (non-pregnant) animals. However, differences in blood acetaldehyde levels measured in pregnant and control animals were not apparent when blood ethanol concentrations were below 40 mumol/ml.

Acetaldehyde↗