Papers by Randall Commissaris
Federation Proceedings, Mar 27, 1987
Pharmacology, Biochemistry and Behavior, Oct 1, 1980
PubMed, Mar 1, 1982
ABSTRACT The nature of the tolerance developed to the hypothermic effects of pentobarbital (PB) a... more ABSTRACT The nature of the tolerance developed to the hypothermic effects of pentobarbital (PB) after short-term chronic administration of this agent was determined in female rats. Rectal temperature was determined in animals maintained on either a chronic PB or control regimen. The chronic PB treatment consisted of 6 days of twice-daily i.p. injections (30 mg/kg each) of PB plus ad libitum feeding of ground chow containing 2.0 mg of PB per g. Controls were administered ground chow and saline injections. After 7 days, control animals manifested a dose-dependent decrease in body temperature after various i.p. test doses (10, 14.2, 20, 28.4 and 40 mg/kg) of PB. Subjects receiving chronic PB administration showed an attenuation of the hypothermic effect, as indicated by a significant shift to the right in the dose-response curve for the test doses in this group. Gas chromatographic analysis of plasma levels in these two groups after i.p. administration of 20 mg/kg of PB resulted in T( 1/2 ) values of 150 and 18 min for control and chronic PB-treated subjects, respectively. Thus, as expected, the chronic PB treatment had enhanced its own metabolism. Regression analysis of the change in body temperature vs. the log of the brain PB concentration (as determined by gas chromatography) resulted in highly significant correlations for both chronic PB-treated and control subjects, and these regression lines did not differ from one another. These data indicate that chronic PB administration over a 1-week period results in pronounced tolerance to the hypothermic effects of this agent, and this conclusion is supported by the decrease in the plasma T( 1/2 ) values for PB in the chronically-treated group and the lack of difference in hypothermic responses between the groups at equivalent brain concentrations of PB.
Pharmacology, Biochemistry and Behavior, Mar 1, 1988
Typical barbiturates produce a spectrum of behavmral effects, including anti-convulsant, muscle r... more Typical barbiturates produce a spectrum of behavmral effects, including anti-convulsant, muscle relaxant, sedaUve hypnoUc and anU-anx~ety actions In contrast to these typical barbiturates, there exists a group of barbiturates which are pro-, rather than antl-convulsant The effects of these convulsant barbiturates on anxiety-related behaviors have not been examined Therefore, the present studies were designed to compare the effects of the convulsant barbiturate CHEB to those of a number of typical barbiturates in the Conditioned Suppression of Dnnklng (CSD) paradigm, an "ammal model" for the study of anxiety and ant~-anxiety agents In dady 10-minute sessions, water-deprived rats were trained to dnnk from a tube which was occasionally electrified (0 5 mA), electnficaUon being signalled by a tone Within 3-4 weeks control responding had stabilized (10-15 shocks and 10-15 ml water/session), drug tests were then conducted at weekly intervals Consistent with previous reports, typical barbiturates (pentobarbltal, secobarbttal, phenobarbital) produced dose-dependent increases in the number of shocks received at doses which did not depress background responding (water retake) In contrast, sub-convulsant doses of CHEB (0 3-2 5 mg/kg) produced a dose-dependent depression of both punished responding and background responding Finally, it was found that pre-treatment with 1 25 mg/kg CHEB did not alter the anti-conflict effects of pentobarbital These results suggest that (1) convulsant and typical barbiturates have markedly different effects on conflict behavmr m the rat and (2) CHEB appears not to possess any "barbiturate antagonist" qualities Barbiturates Convulsants CHEB Conflict behavior Anxiety
PubMed, Nov 1, 1986
Manganese (Mn) is an industrially important metal which, when given in excess, produces lesions i... more Manganese (Mn) is an industrially important metal which, when given in excess, produces lesions in the basal ganglia of rats and humans. Humans poisoned with Mn often exhibit an initial hyperactivity ("manganese madness") followed by a parkinsonian-like syndrome. The present studies examined the effects of chronic Mn exposure on locomotor activity in rats maintained on 0.0 or 1.0 mg Mn(Cl)2 X 4H2O/ml drinking water. No differences in mean body weights were observed from 0-65 weeks of treatment. Locomotor activity was tested in 15 min sessions at weekly intervals (Weeks 1-13), then at 4 or 14 week intervals thereafter. Mn treatment produced a significant increase in activity on weeks 5-7 before returning to control values at 8 weeks. Habituation measured within a test session was not affected at any time. At 14 and, to a lesser extent, 29 weeks, Mn animals were found to be more responsive to the effects of 1.25 mg/kg d-amphetamine (d-A) than controls. This increased responsiveness was gone at Weeks 41 and 65. Consistent with clinical reports, these results suggest that Mn may produce a transient increase in dopaminergic function, as measured by both spontaneous and d-A-stimulated locomotor activity.
Pharmacology, Biochemistry and Behavior, May 1, 1981
Psychopharmacologia, 1988
Pharmacol Biochem Behav, 1992
PubMed, Oct 1, 1981
R. L. COMMISSARIS,2'3 W. H. LYNESS,4 K. E. MOORE and R. H. RECH ... Department of Pharmacolo... more R. L. COMMISSARIS,2'3 W. H. LYNESS,4 K. E. MOORE and R. H. RECH ... Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan ... ABBREVIATIONS: 5-HT, 5-hydroxytryptamine; FR-40, fixed-ratio 40; LSD, d-Iysergic acid diethylamide; DMT, ...
Birkhäuser Basel eBooks, 1991
The effects of long-term chronic post-test treatment with numerous typical (e.g., imipramine, des... more The effects of long-term chronic post-test treatment with numerous typical (e.g., imipramine, desipramine, phenelzine) or atypical (alprazolam, trazodone, mianserin, buproprion) antidepressants on conflict behaviour in rats were determined. Chronic treatment with most agents (exceptions: mianserin, buproprion) resulted in a gradually-developing anti-conflict effect, with a latency to onset of 3–5 weeks. These data suggest that animal conflict paradigms might be effective animal procedures for studying the anxiolytic and/or anti-panic effects of antidepressant agents.
Psychopharmacology, Oct 1, 1982
This study examined the effects of various drug treatments (IP injections) proposed to modify cen... more This study examined the effects of various drug treatments (IP injections) proposed to modify central 5-hydroxytryptamine (5-HT) activity on a conditioned suppression of drinking behavior in water-deprived rats. The subjects were trained to drink their daily water requirement during a 10-min session. Intermittent tone periods of 7 s were then introduced, the last 5 s of which the drinking tube was electrified. The animals gradually suppressed tube contacts during the tone to a low constant level within 2 weeks of training. Diazepam increased punished responding dramatically. The 5-HT antagonists methysergide (1 - 18 mg/kg), cyproheptadine (1 - 18 mg/kg), metergoline (0.25 - 2.0 mg/kg) and cinanserin (10 - mg/kg) failed to induce large, reliable increases in punished responding. When a low dose of diazepam was combined with 5-HT antagonists, only one treatment, methysergide at 3 mg/kg, potentiated the anticonflict activity of diazepam. Acute or chronic treatment with PCPA increased behavior suppressed by punishment, but this effect was weak, brief, and poorly related to the depletion of brain 5-HT. LSD (0.3 - 100 microgram/kg) administered 1, 10, or 30 min before the test was ineffective in overcoming suppression by punishment. Mescaline (6 - 30 mg/kg) had no significant effect on punished responding. 5-HTP (18 mg/kg) decreased the number of shocks accepted, but not after pretreating with carbidopa. Pretreatment with carbidopa plus 5-HTP potentiated the anticonflict effect of diazepam. The 5-HT agonist mCPP (0.25 - 2.0 mg/kg) enhanced suppression due to punishment, but only in doses that interfered with unpunished responding. The 5-HT-releasing agent fenfluramine (0.25 - 1.0 mg/kg) did not affect this behavior. Amitriptyline pretreatment in a dose not affecting unpunished behavior (5.6 mg/kg) potentiated the diazepam-induced increase in punished responding. These results are difficult to reconcile with the proposal that suppression of behavior consequent to punishment is related to brain 5-HT activity.
Pharmacology, Biochemistry and Behavior, Jun 1, 1993
Pharmacology, Biochemistry and Behavior, Mar 1, 1989
Female Maudsley Reactive (MR/Har) and Nonreactive (MNRA/Har) rats were tested for initial acousti... more Female Maudsley Reactive (MR/Har) and Nonreactive (MNRA/Har) rats were tested for initial acoustic startle reactivity and within-session startle habituation. Subjects were exposed in each of five weekly sessions to 12 acoustic startle noise bursts at a 20-s interstimulus interval, a procedure in which genetically heterogeneous Sprague Dawley rats have been shown to exhibit robust within-session habituation. Although initial startle reactivity was comparable in the two strains, significant differences in withinsession habituation were observed. Specifically, MR~Hat rats were observed to exhibit substantial within-session habituation to these acoustic stimuli, while rats of the MNRA/Har strain exhibited little, if any, habituation to these repeated acoustic stimuli. The basis for this dramatic difference in within-session startle habituation in these MaudsIey rats is at present unexplained and under investigation.
Psychopharmacology, Mar 1, 1982
The effects of diazepam quipazine, lysergic acid diethylamide (LSD), and 2,5-dimethoxy-4-methylam... more The effects of diazepam quipazine, lysergic acid diethylamide (LSD), and 2,5-dimethoxy-4-methylamphetamine (DOM) were examined on a conditioned suppression paradigm. Food-deprived rats were trained to drink a liquid diet from a tube. Subsequently, intermittent 7-s tones were presented during the daily 10-min sessions, the tube being electrified during the last 5 s of each tone. The subject gradually learned to suppress
Behavioural Pharmacology, Mar 1, 1995
Conflict behavior in rats was examined over the course of several weeks of chronic treatment with... more Conflict behavior in rats was examined over the course of several weeks of chronic treatment with selective and non-selective monoamine oxidase inhibitors (MAOIs). In daily 10min sessions, rats were trained to drink from a tube which was occasionally electrified (0.5mA). Electrification was signalled by the presence of a tone. Within 3-4 weeks, control (i.e. non-drug) conflict behavior had stabilized (30-40 shocks and 8-12ml water/session) and drug testing began. Chronic administration (two injections/day for 8 weeks) with a non-selective (i.e. MAO-A and MAO-B inhibiting) dose of pargyline (15mg/kg) resulted in a time-dependent increase in punished responding. In contrast, chronic administration of the MAO-A selective inhibitor (clorgyline; 1.0mg/kg, 2mg/kg), the MAO-B selective inhibitor deprenyl (5mg/kg) or MAO-B inhibiting doses of pargyline (1.0mg/kg, 5mg/kg) were without effect. Finally, chronic treatment with the combination of a low dose of clorgyline (1.0mg/kg) and a low dose of pargyline (1.0mg/kg) did result in a time-dependent increase in punished responding. These results suggest that inhibition of both MAO-A and MAO-B is required for the eventuation of the anxiolytic effect resulting from chronic MAOI treatment.
Pharmacology, Biochemistry and Behavior, Nov 1, 1992
Pre-versus postsynaptic receptor mechanisms. PHARMACOL BIOCHEM BEHAV 43(3) 697-704, 1992.-The eff... more Pre-versus postsynaptic receptor mechanisms. PHARMACOL BIOCHEM BEHAV 43(3) 697-704, 1992.-The effects of acute pretest administration and chronic posttest administration of clonidine or the selective ot 2adrenoceptor agonist UK-14,304 on conflict behavior were investigated. In daily 10-rain sessions, water-deprived rats were trained to drink water from a tube that was occasionally electrified (0.25 mA); electrification was signaled by a tone. Prior to treatment, subjects accepted 25-30 shocks/session (punished responding) and consumed approximately 12-15 ml/session (unpunished responding). Acute pretest administration of clonidine or UK-14,304 did not increase punished responding. In contrast, chronic posttest clonidine administration (40 #g/kg, IP, twice daily for 8 weeks) resulted in a robust and timedependent increase in punished responding (60-70 shocks/session) relative to saline-treated controls. Moreover, the selective ct2-adrenoceptor agonist UK-14,304 also increased punished responding when administered chronically (1.0 mg/kg, BID). Administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine HC1 (DSP4, 65 mg/kg, IP) significantly decreased punished responding in control conditioned suppression of drinking sessions. The anticonflict effect associated with chronic posttest clonidine treatment was not altered by DSP4 pretreatment. These findings suggest that chronic posttest c~2-adrenoceptor agonist treatment produces an anticonflict effect independent of its actions at presynaptic c~2-adrenoceptors.
Pharmacology, Biochemistry and Behavior, Nov 1, 1988
Conditioned Suppression of Drinking (CSD) paradigm is an "animal model" for anxiety which has bee... more Conditioned Suppression of Drinking (CSD) paradigm is an "animal model" for anxiety which has been used to study the anticonflict effects of the benzodiazepines. It has been postulated that benzodiazepines produce their effects through interactions with GABA. The present study examined this potential GABA-BZ interaction on CSD behavior. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA), electrification being signalled by a tone. Within 2-3 weeks control CSD responding had stabilized (16-24 shocks session and 10-14 ml water/session); drug tests were conducted at weekly intervals. As expected, diazepam (0.3-20.0 mg/kg), pentobarbital (0.6-10.0 mg/kg) and phenobarbital (10.0-40.0 mg/kg) alone markedly increased the number of shocks received at doses which did not depress background responding (i.e., water intake). Treatment with the GABA-transaminase inhibitor aminooxyacetic acid (AOAA: 2.5-10.0 mg/kg, 10-or 60-minute pretreatment) alone had no anticonflict effect on CSD behavior. However, pretreatment (60-minute) with 10.0 mg/kg AOAA significantly potentiated the effects of diazepam, as indicated by a significant shift to the left in the diazepam dose-response curve relative to diazepam alone. By contrast, the anticonflict effects of pentobarbital and phenobarbital were unaffected by this AOAA pretreatment. Thus, while increases in GABA transmission alone do not appear to affect CSD behavior, the anticonflict effects of benzodiazepines, but not barbiturates, appear to be potentiated by increases in GABA transmission.
PubMed, Mar 1, 1998
Lister hooded rats exhibit bursts of locomotion when exposed to a 20 kHz acoustic stimulus; this ... more Lister hooded rats exhibit bursts of locomotion when exposed to a 20 kHz acoustic stimulus; this ultrasound-induced locomotion has been suggested as a potential model for panic attacks. The present studies determined the effects of treatment with the convulsant agents strychnine and pentylenetetrazole and the anticonvulsant agents pentobarbital and ethosuximide on locomotor behaviour elicited by experimenter-presented ultrasounds in Lister hooded rats. Behaviour in a circular arena was viewed live and tracked electronically. In Experiment 1, brief exposure to an ultrasound stimulus typically resulted in short intensity-related bursts of locomotion in control rats. Pentobarbital or ethosuximide treatment reduced this short-term ultrasound-induced locomotion in a dose-related manner, whereas pentylenetetrazole or strychnine treatment increased these locomotor bursts. In Experiment 2, exposure to the ultrasound stimulus for a longer period resulted in irregular cycles of bursts of locomotion followed by periods of relative inactivity in control rats. In addition, approximately 10% of control rats exhibited convulsions associated with this long-duration ultrasound exposure at 98 dB sound pressure level. Sub-convulsant doses of the convulsant treatments increased the frequency of occurrence of convulsions associated with the ultrasound stimulus; pentobarbital or ethosuximide pretreatment significantly reduced this effect. The present findings suggest that a relationship exists between ultrasound-induced locomotor bursts and convulsant activity.
Pediatric Infectious Disease Journal, Aug 1, 1987
Pharmacology, Biochemistry and Behavior, Nov 1, 1983
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Papers by Randall Commissaris