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A C Collins

Publications and source records attributed to A C Collins.

At least 145 records · Page 8Linked to original sources
PubMed1986

Mecamylamine blockade of nicotine responses: evidence for two brain nicotinic receptors.

Mice of two inbred strains, DBA and C3H, were pretreated with mecamylamine before challenge with nicotine. Mecamylamine blocked nicotine-induced seizures, enhanced startle, and alterations in respiratory rate, Y-maze activity, heart rate and body temperature. Mecamylamine blocked nicotine-induced seizures and enhanced startle with IC50 values of less than 0.1 mg/kg. The other nicotine effects were blocked by mecamylamine with IC50 values between 0.8 and 2.3 mg/kg. Strain differences in sensitivity to mecamylamine blockade were also detected. These results suggest that nicotine elicits its effects at two receptors, which may be those labeled with [125I]-alpha-bungarotoxin and with [3H]-nicotine.

Animals↗
PubMed1986

A genetic analysis of nicotine effects on open field activity.

The genetics of the effects of nicotine on the open field activity of mice were studied using a 5 by 5 diallel cross. The five inbred strains used were: A, BALB, C57BL, DBA, and C3H. These strains differ both in basal open field activity as well as activity after injection of nicotine. Analysis of the results of baseline activity indicated that both additive and dominance variance affected the activity of the animals. The dominance was non-directional. Likewise, the responses observed after injection of 0.75 mg/kg nicotine displayed both additive and dominance components. However, after correcting the results for differences in basal activity, the dominance item was primarily directional. This directional dominance was towards a more intense response to the effects of the drug, that is, a decrease in open field activity.

Animals↗
PubMed1986

Quantification of physiological and behavioral measures of alcohol withdrawal in long-sleep and short-sleep mice.

A quantitative, multidimensional animal model of the alcohol withdrawal syndrome is desirable for investigating individual differences in susceptibility to alcohol dependence. Following exposure to control or ethanol diets for 7 or 14 days, we measured respiration rates, body temperature, acoustic startle responses, and heart rates in Long-Sleep (LS) and Short-Sleep (SS) mice to determine how initial alcohol sensitivity influences dependence liability. SS mice consumed a greater amount of ethanol diet and exhibited a more severe withdrawal syndrome than LS mice. Withdrawal severity resulted from an interaction of genotype with duration of ethanol exposure. The abstinence syndrome was generally characterized by depressed behavioral and physiological functioning for both mouse lines. Initial alcohol sensitivity influenced the rate of alcohol increase in the blood during dependence induction which, in turn, influenced withdrawal severity. This model incorporates several discriminative measures that independently assess withdrawal reactions and provides a useful animal model of alcohol withdrawal.

Animals↗
PubMed1986

Nicotinic binding sites in rat and mouse brain: comparison of acetylcholine, nicotine, and alpha-bungarotoxin.

The properties of the binding sites for radiolabeled acetylcholine (measured in the presence of atropine), nicotine, and alpha-bungarotoxin were compared in brain tissue prepared from both rat and mouse. These three binding sites were tested for the following properties: affinity and density of ligand binding, effects of competitive inhibitors, regional distribution, effects of treatment with dithiothreitol and the reversal of these effects by treatment with 5,5'-dithiobis(2-nitrobenzoic acid), thermal lability, effects of protease treatment, and response to chronic administration of nicotine in vivo. The binding sites for acetylcholine and nicotine were affected identically for all measurements, whereas the binding site for alpha-bungarotoxin was affected in a manner different from that for the other two ligands. Although the regional distribution of nicotine and acetylcholine binding differed between rat and mouse brain, other properties of this binding site were very similar between the two species. The results are consistent with the proposal that acetylcholine and nicotine bind to the same sites in both rat and mouse brain, whereas alpha-bungarotoxin binds to different sites.

Acetylcholine↗
PubMed1986

Nicotine-induced tolerance and receptor changes in four mouse strains.

The effects of chronic infusion of 3.0 mg/kg/hr of nicotine on the behavioral responses of four mouse strains (C3H, C57BL, BALB and DBA) to challenge doses of nicotine and on the levels of cholinergic receptors and enzymes were determined. Mice of the C57BL, BALB and DBA strains developed tolerance to the effects of nicotine on Y-maze activity, Y-maze rearing and body temperature. The C3H mice did not exhibit any evidence of tolerance to the effects of nicotine on these measures, but this strain did show tolerance to the effects of nicotine on acoustic startle response. None of the strains developed tolerance to the effects of nicotine on respiration rate, and only the BALB mice demonstrated tolerance to nicotine-induced bradycardia. Chronic nicotine treatment also elicited changes in putative brain nicotinic receptors. Increased binding of L-[3H]nicotine was seen in six brain regions in all four mouse strains. The changes in binding were similar for all the strains. The binding of alpha-[125I]bungarotoxin was also elevated in the four mouse strains, and modest differences among the strains were evident in this measure, with the C3H strain showing the smallest increases in four of the six brain regions. Chronic nicotine treatment did not alter brain muscarinic receptors, as measured with L-[3H]quinuclidinyl benzilate binding, nor were the activities of acetylcholinesterase or choline acetyltransferase altered, except that a small change in hippocampal choline acetyltransferase activity may have occurred. These results indicate that tolerance to nicotine is regulated by genetic factors and that changes in brain nicotinic receptor numbers are not sufficient to explain the development of tolerance.

Acetylcholinesterase↗
PubMed1986

Differential effects of central nervous system depressants in long-sleep and short-sleep mice.

The relative sleep time response of long-sleep (LS) and short-sleep (SS) mice was determined after the i.p. injection of varying doses of several anesthetic agents that vary in lipid solubility. The LS and SS mice were bred selectively for differences in duration of ethanol-induced sleep time. The drugs tested included: several halogenated ethanol derivatives (trifluoro-, trichloro-, tribromo- and dichloroethanol), chloral hydrate, paraldehyde, urethane and the water soluble barbiturates, barbital and phenobarbital. The LS mice slept for a longer time after the i.p. injection of the majority of these drugs than did the SS. As the lipid solubility of the agents increased, the response differential decreased. These data indicate that the LS and SS mice do not differ only in response to alcohols. Rather, they differ in sensitivity to agents that have lipid solubilities which resemble that of ethanol. Furthermore, these data imply that anesthetic agents with low lipid solubility have different mechanisms of action than do anesthetic agents with high lipid solubility.

Alcohols↗
PubMed1986

Dose-response analysis of nicotine tolerance and receptor changes in two inbred mouse strains.

Mice of two inbred strains, DBA and C3H, were infused i.v. with saline, or 2, 4 or 6 mg/kg/hr of nicotine for 10 days. Two hours after termination of infusion the mice were challenged with one of several nicotine doses and the effects on respiration rate, Y-maze activity and rears, acoustic startle response, heart rate and body temperature were measured. Saline-infused C3H mice were less responsive than were DBA mice for all these tests with the exception of the acoustic startle response test. Nicotine-treated DBA mice developed a dose-related tolerance for most measures, whereas C3H mice did not appear to develop tolerance to any measure until the infusion dose reached 4 mg/kg/hr. The two mouse strains did not differ in the number of [3H] nicotine binding sites in six brain regions, and chronic nicotine treatment elicited similar changes in the binding of this ligand in the two strains. C3H mice had greater concentrations of alpha-[125I] BTX binding in hippocampus, midbrain and hypothalamus than did DBA mice. Chronic nicotine treatment resulted in an identical increase in bungarotoxin binding in the two mouse strains such that the initial strain differences were maintained. These results indicate that a threshold in drug response must be surpassed before a mouse develops tolerance to nicotine. In addition, mechanisms other than differences in receptor numbers must be invoked to explain differences in response to nicotine.

Animals↗
PubMed1986

Genetic analysis of nicotine-induced seizures and hippocampal nicotinic receptors in the mouse.

A classical F2 and backcross genetic design was used to examine the relationship between sensitivity to nicotine-induced seizures and hippocampal nicotinic receptors. Nicotine was administered by i.v. infusion through cannulas implanted in the right jugular veins of mice from the C3H and DBA mouse strains and their derived F1, F2 and backcross (F1 X C3H and F1 X DBA) generations. Nicotine-induced seizure sensitivity was assessed by infusing nicotine at a 2.0 mg/kg/min concentration until the onset of a clonic seizure. After seizure testing, mice were sacrificed and the binding of alpha-bungarotoxin (BTX) was determined in three brain regions: cortex, midbrain and hippocampus. The pattern of results for the six generations for seizure sensitivity was similar to that observed for hippocampal BTX binding. Genetic analyses indicate that receptor concentrations in the hippocampus and seizure sensitivity are both influenced by a relatively simple genetic system which involves one or more genes acting in an additive fashion. In addition, the genetic correlation which is indicative of the extent to which two characters are influenced by the same genes, supports the relationship between nicotine-induced seizure sensitivity and hippocampal BTX binding. The results suggest that those animals which are sensitive to nicotine-induced seizures have a greater concentration of nicotinic receptors as determined by the binding of BTX than animals which are less sensitive to the convulsant effects of nicotine.

Animals↗
PubMed1985

Relationship between nicotine-induced seizures and hippocampal nicotinic receptors.

A controversy has existed for several years concerning the physiological relevance of the nicotinic receptor measured by alpha-bungarotoxin binding. Using mice derived from a classical F2 and backcross genetic design, a relationship between nicotine-induced seizures and alpha-bungarotoxin nicotinic receptor concentration was found. Mice sensitive to the convulsant effects of nicotine had greater alpha-bungarotoxin binding in the hippocampus than seizure insensitive mice. The binding sites from seizure sensitive and resistant mice were equally affected by treatment with dithiothreitol, trypsin or heat. Thus it appears that the difference between seizure sensitive and insensitive animals may be due to a difference in hippocampal nicotinic receptor concentration as measured with alpha-bungarotoxin binding.

Animals↗
PubMed1985

Brain arachidonic acid metabolites. Functions and interactions with ethanol.

The formation and potential function of arachidonic acid metabolites in brain are reviewed briefly. Cyclooxygenase metabolites of arachidonic acid are formed in brain, but the lipoxygenase derivatives have not been demonstrated. Evidence clearly indicates that the cyclooxygenase products act as neuromodulators. Possible effects of leukotrienes on brain function remain in doubt, although several studies have suggested a role for the leukotrienes and it appears that these agents have a long-lasting effect. Potential interactions between ethanol and brain arachidonic acid metabolites have received minimal attention. Several studies indicate that pretreatment with prostaglandin synthetase inhibitors produces antagonism of ethanol's behavioral effects. These observations may be related to preliminary findings that ethanol increases brain prostaglandin content.

Animals↗
PubMed1985

Indomethacin antagonism of ethanol-induced sleep time: sex and genotypic factors.

Pretreatment with prostaglandin synthetase inhibitors (PGSI) significantly decreases the CNS effects of ethanol across the entire ethanol dose-response curve. PGSIs do not significantly affect ethanol metabolism. These effects have been shown in HS/Ibg, LS/Ibg, and SS/Ibg males and females. These strains of mice are useful in alcohol research but are not widely available. The present study examined the possibility of similar effects in C57BL/6 and C3H/2 mice of both sexes. PGSI pretreatment significantly reduced ethanol sleep time across both sexes and genotypes in a dose-dependent manner. Females of both strains required more PGSI to antagonize ethanol's actions relative to males. Within sex, mice with greater sensitivity to ethanol required more PGSI to optimally reduce sleep time than less sensitive mice. These results extend previous findings, and support our hypothesis that one of ethanol's primary mechanisms of action in the CNS is to increase the synthesis of prostaglandins.

Animals↗
PubMed1985

Genetically determined differences in acute responses to diisopropylfluorophosphate.

The acute effects of diisopropylfluorophosphate (DFP) were assessed in DBA/2Ibg, C57BL/6Ibg and C3H/2Ibg mice. The DFP was administered by intraperitoneal injection in saline. Brain acetylcholinesterase (AChE) activity was maximally inhibited within 5 min after injection. All mice showed signs of organophosphate intoxication including salivation, lacrimation, diarrhea, respiratory distress, tremor and, at high doses, seizures. The C57BL mice were most susceptible to these effects of DFP. The LD50 values for DFP were 8.0, 7.6, and 6.8 mg/kg for male DBA, C3H, and C57BL mice, respectively. The LD50 values for females were nearly the same. Body temperature and brain AChE activity decreased in a dose-dependent manner following injections of DFP of 3.17, 4.22, 5.28, and 6.33 mg/kg. Maximum temperature depression occurred 2 hours after DFP administration; by 24 hours temperatures had returned to normal except for C57BL mice treated with the highest dose of DFP. The C57BL strain was most susceptible to the DFP-induced hypothermia, the C3H strain was the most resistant, and the DBA strain was intermediate. Maximum temperature depression and residual AChE activity, as measured 24 hours after injection, were linearly related. These strain differences do not seem to be explained easily by a differential inhibition of AChE activity.

Animals↗
PubMed1985

Tolerance, cross-tolerance, and receptors after chronic nicotine or oxotremorine.

Saline, 8.0 mg/kg/hr nicotine, or 1.0 mg/kg/hr oxotremorine was continuously infused into the jugular veins of DBA female mice. After 10 days of treatment, respiratory rate, Rotarod performance, Y-maze crossings, Y-maze rears, heart rate, and body temperature were measured after challenge with 2.0 mg/kg nicotine or saline or 0.2 mg/kg oxotremorine. Nicotine-infused mice were tolerant to the effects of nicotine for all six tests and oxtremorine-infused mice were tolerant to the effects of oxotremorine for all six tests and to the effects of nicotine on heart rate and body temperature. Oxotremorine infusion reduced the Bmax for [3H]-L-QNB binding, but had no effect on Bmax for either [3H]-DL-nicotine or [125I]-alpha-BTX binding. Conversely nicotine infusion did not alter the Bmax for [3H]-L-QNB binding, but increased the Bmax for both [3H]-DL-nicotine and [125I]-alpha-BTX binding. These results indicate that tolerance developed to the effects of two cholinergic agents, nicotine and oxotremorine, and that some cross-tolerance to the effects of nicotine occurred in oxotremorine-treated mice. Treatment with oxotremorine caused down-regulation of muscarinic receptors, while treatment with nicotine caused up-regulation of nicotinic receptors. Although some cross-tolerance to the effects of nicotine occurred in oxotremorine-treated mice, this did not appear to result from changes in nicotinic receptors.

Animals↗
PubMed1985

A test battery for measuring nicotine effects in mice.

A test battery consisting of measurement of respiration, startle response, Y-maze activity, heart rate, and body temperature has been developed to assess the effects of nicotine on the mouse. Results obtained using the test battery were compared to those obtained with each test individually in four inbred strains of mouse (BALB, C57BL, DBA and C3H). No significant differences between the results obtained using the test battery and those obtained with individual tests were found. The results did demonstrate, however, that the genotype of the mouse strongly influenced the responses in several of the tests.

Animals↗
PubMed1985

Sample preparation and radioimmunoassay for circulating free and antibody-bound insulin concentrations in insulin-treated diabetics: a re-evaluation of methods.

Methods for blood sample preparation and radioimmunoassay of free and antibody-bound serum or plasma insulin concentrations, using polyethylene glycol (PEG) solution to precipitate bound insulin, have been evaluated and compared. Method A was rapid mixing of whole blood with PEG, followed by separation of bound insulin by centrifugation into Ficoll; method B was rapid PEG addition to whole blood, followed by centrifugation alone; method C was conventional PEG addition to thawed plasma or serum, followed by centrifugation to remove bound insulin. Method A was found to have acceptable performance and reproducibility; serum free insulin levels were not significantly different from those measured by the simpler method B. In samples from insulin-dependent diabetics, serum free insulin was significantly higher and bound insulin significantly lower in method A compared to the conventional method C. However, in samples from non-diabetics there was no significant difference between methods A and C. Spurious results were obtained by addition of PEG and assay of plasma and serum samples after either freezing and thawing or incubation at 37 degrees C for 2h, compared to PEG addition and assay of fresh plasma or serum samples. We conclude that conventional, delayed addition of PEG to plasma or serum may result in redistribution of free and bound insulin and that values more representative of in vivo blood insulin levels are obtained by rapid PEG addition methods.

Diabetes Mellitus↗
PubMed1985

Time course study of the effects of chronic nicotine infusion on drug response and brain receptors.

The experiments reported here examined the time course of the development and loss of tolerance to nicotine as well as the time course for the up-regulation and return to basal levels of brain nicotinic receptors. Nicotine was administered by continuous i.v. infusion through cannulae implanted in the right jugular veins of DBA mice. Tolerance to the effects of nicotine on Y-maze activity and rears, body temperature and heart rate was seen accompanying the infusion of 4 mg/kg/hr of nicotine. Maximal tolerance was obtained in 4 days and was paralleled by increases in the number of brain nicotine binding sites. The binding of alpha-bungarotoxin was also increased by chronic nicotine treatment but increases in binding preceded the development of detectable tolerance to the challenge dose of nicotine. Chronic nicotine treatment had no effect on quinuclidinyl benzilate binding. Tolerance to the effects of nicotine was lost at different rates for the various tests in that base-line response was attained for the Y-maze activity and rearings test in 8 days, whereas 12 to 16 days were required to regain control response for the body temperature test. Tolerance for the heart rate test persisted throughout the 20-day withdrawal period. Brain nicotine binding sites had returned to control levels by 8 days after treatment whereas the alpha-bungarotoxin binding sites were at control levels at the earliest time of postinfusion testing (4 days). Brain quinuclidinyl benzilate binding sites were unaffected by nicotine treatment and did not change during the withdrawal period. The changes in nicotine binding in the various brain regions during the onset and offset experiments were virtually identical. These changes in binding correlated highly with the acquisition and loss of tolerance to the effects of nicotine on the Y-maze locomotor activity and body temperature tests. The correlations between changes in nicotine binding and the Y-maze rearings and the heart rate tests were lower but some association is suggested. Although changes in nicotine binding may explain some of the tolerance observed, other explanations for tolerance must be sought as well.

Animals↗