Biomedical subjects

L Logan

Publications and source records attributed to L Logan.

35 records · Page 2Linked to original sources

PubMed1989

Effects of caffeine, cocaine and their combination on fixed-interval behavior in rats.

The effects of the central nervous system stimulants, caffeine and cocaine, on schedule-controlled behavior were determined in rats trained to perform a fixed-interval (FI) 5-minute task. When given alone caffeine produced a doubling of FI response rate at a dose of 10 mg/kg and reduced responding at a dose of 32 mg/kg. Cocaine, which was also expected to increase FI responding, did not increase response rate at doses of 3.2 or 10 mg/kg and decreased the rate of responding at a dose of 32 mg/kg. Caffeine had minimal effects on quarter life and appeared to increase local rates of responding across the interval. Cocaine decreased quarter life dramatically at a dose that had no effect on overall response rate. Local rates of responding were increased early in the interval and decreased in the later segments. The effects of both drugs were found to be rate-dependent. When these compounds were given in combination the results obtained appeared to be related to the rate of responding that caffeine alone would produce.

Animals↗

PubMed1988

Effects of chronic amphetamine in BALB/cBy mice, a strain that is not stimulated by acute administration of amphetamine.

The effects of d-amphetamine and methylphenidate on locomotor activity of BALB/cByJ mice were evaluated. d-Amphetamine had no effect or inhibited locomotor activity at acute doses of up to 10 mg/kg while methylphenidate stimulated locomotor activity at acute doses between 10 and 32 mg/kg. The dose-response curves for methylphenidate and d-amphetamine appeared to be quantal in nature. During a 21-day chronic treatment with 10 mg/kg d-amphetamine no evidence of tolerance to the depressant effects of relatively high doses of d-amphetamine was observed. However, a 3.2 mg/kg dose of d-amphetamine, which acutely inhibited locomotor activity, was found to stimulate locomotor activity following chronic amphetamine treatment. Doses of methylphenidate which acutely stimulated activity were without effect in mice chronically receiving amphetamine. Although the mechanism underlying these behavioral effects has yet to be established, our results indicate that inherent alterations can differentially affect both acute and chronic susceptibility to the behavioral effects of amphetamine and methylphenidate. Use of such altered strains of mice can be especially revealing of subtle behavioral effects brought about by chronic drug treatment which are not readily demonstrated following acute administration of amphetamine.

Animals↗

PubMed1986

Inherent differences in sensitivity to methylxanthines among inbred mice.

The behavioral effects of caffeine, theophylline, paraxanthine, and theobromine on locomotor activity were analyzed in four strains of inbred mice that were previously shown to differ in their acute toxic responses to caffeine administered at high dosages. Dose response curves for the effects of caffeine, theophylline, paraxanthine and theobromine on locomotor activity were established in CBA/J, C57BL/6J, DBA/2J and SWR/J strains of inbred mice. Paraxanthine was the maximally effective methylxanthine in the CBA/J, DBA/2J and SWR/J strains, while in the C57BL/6J strain, caffeine was the maximally effective methylxanthine. Theophylline failed to stimulate locomotor activity in the C57BL/6J strain and theobromine failed to stimulate activity in all of the strains tested. Decreases in locomotor activity were seen at the 100 mg/kg dose of caffeine in the C57BL/6J mice and at the 100 mg/kg dose of theophylline in the C57BL/6J, DBA/2J and SWR/J strains. Theobromine produced decreases in locomotor activity in the C57BL/6J, DBA/2J and SWR/J strains of mice. In contrast to the other methylxanthines, paraxanthine failed to decrease activity across the range of doses tested (1.0-150 mg/kg). These data suggest that the methylxanthines have genetically specified multiple modes of action upon locomotor activity and that the use of genetically distinct strains of mice may have important value in the neurochemical and pharmacological dissection of methylxanthine-induced behavioral effects.

Animals↗

PubMed1986

Complex genetic determinants of susceptibility to methylxanthine-induced locomotor activity changes.

The intent of this study was to investigate the role of inheritance in the determination of susceptibility to methylxanthine-induced behavioral changes. Two strains of inbred mice, SWR and CBA, which differ significantly in their response to caffeine- and theophylline-induced stimulation of locomotor activity, were used in classical genetic crosses to produce reciprocal F1 hybrids, reciprocal backcross progeny F2 progeny. Theophylline dose response curves in the reciprocal F1 hybrid strains were identical to each other and to their methylxanthine-responsive (CBA) parent. These results indicated that theophylline responsiveness behaved as a simple autosomal dominant trait. Behavioral responses of these F1 hybrid strains to caffeine showed the same maximal enhancement of locomotor activity as their CBA progenitor at a dose 10 mg/kg IP, but locomotor activity stimulation also occurred at 32 mg/kg IP, a dose which inhibited their CBA parent. These data suggest that the genes specifying caffeine responsiveness differ from those encoding theophylline responsiveness. For both caffeine and theophylline, behavioral phenotypes and their expected frequencies of occurrence among backcross and F2 progeny differed significantly from the segregation ratios expected for a trait determined by a single gene. These non-Mendelian segregation ratios suggest that locomotor activity stimulation by both of these methylxanthines is polygenically determined. It was anticipated that the same genetically encoded neurochemical mechanism would underlie the difference in behavioral response to the two methylxanthines. However, no significant correlation between caffeine-induced and theophylline-induced stimulation of locomotor activity was observed among progeny derived from backcrosses of F1 self-crosses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Differential antagonism of the behavioral depressant and hypothermic effects of 5'-(N-ethylcarboxamide) adenosine by theobromine.

The methylxanthine, theobromine (3,7-dimethylxanthine), was tested in mice, to determine whether theobromine could function in vivo as an adenosine receptor antagonist, in keeping with its reported in vitro effects as a blocker of agonist binding to the adenosine A-1 receptor. Theobromine doses, which themselves had no direct effects on spontaneous locomotor activity, completely blocked N6-cyclohexyladenosine-induced suppression of locomotor activity but were without effect on 5'-N-ethylcarboxamide adenosine (NECA)-induced decreases in motor activity. In contrast to the specific antagonism, theobromine blocked the hypothermia induced by both of these adenosine analogs. These results demonstrate that theobromine is an active in vivo adenosine receptor antagonist and that the antagonism of N6-cyclohexyladenosine sensitive systems occurs even though theobromine does not stimulate spontaneous locomotor activity. Thus, the behavioral stimulant effects of methylxanthines may be more related to effects on NECA-sensitive systems, which are not blocked by theobromine. The use of in vivo differences in the effects xanthine may provide a useful tool in the development of compounds to probe the mechanisms of caffeine induced CNS effects.

Adenosine↗

PubMed1985

Sensitivity of inbred mice to methylxanthines is not determined by plasma xanthine concentration.

Male CBA/J and SWR/J mice were tested with doses of caffeine, theophylline and 8-p-sulfophenyltheophylline (xanthine). Caffeine produced dose-related decreases in locomotor activity and colonic temperatures in SWR/J mice. However, caffeine produced increases in locomotor activity and failed to lower the body temperature of CBA/J mice. Theophylline produced a decrease in body temperature of SWR/J mice. Comparison of brain caffeine levels demonstrated no difference in brain pharmacokinetics. The peripherally active xanthine failed to alter body temperature at the same molar dose as that of theophylline. These data clearly demonstrate that genetic differences in the effects of methylxanthine are due to inherent differences in the central nervous system sensitivity of the two strains. The data further indicate that while differences in xanthine metabolism may occur in inbred mice, these differences are not a major factor in the acute, peak plasma level, effects of xanthines.

Animals↗

PubMed1984

Antagonism of the behavioral effects of L-phenylisopropyladenosine (L-PIA) by caffeine and its metabolites.

Three male Sprague-Dawley strain rats were trained to respond under a multi-component time out 5 min variable ratio 15 (VR15) schedule of food reinforcement. Cumulative, within session dose-effect curves were determined for L-PIA alone and after methylxanthine pretreatment. L-PIA alone produced dose related decreases on VR15 responding at doses between 0.032 and 0.178 mg/kg. Significant antagonism of L-PIA was demonstrated from pretreatment with caffeine, theophylline, theobromine, paraxanthine, 3-methylxanthine, and 7-methylxanthine. No antagonism of L-PIA was observed following pretreatment with 1-methylxanthine. Consistent with the adenosine receptor blockade hypothesis, caffeine also antagonized the effects of 5'-N-ethylcarboxamide adenosine (NECA) on VR15 responding.

Adenosine↗

PubMed1974