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Biomedical subjects

G A Rowan

Publications and source records attributed to G A Rowan.

17 recordsLinked to original sources
PubMed1994

Discriminative stimulus properties of the benzodiazepine receptor inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM).

The purpose of this study was to determine whether rats could be trained to discriminate the stimulus properties of the benzodiazepine (BZ) receptor inverse agonist DMCM from saline in a conditioned taste aversion paradigm. On a drug trial, water-deprived rats were injected with DMCM (0.55-0.6 mg/kg IP), allowed access to a 0.25% saccharin solution for 30 min, and then injected with LiCl. On non-drug trials, saline injections bracketed the drinking period. Conditioned controls were treated similarly with DMCM and saline on drug and non-drug trials, but received injections of saline instead of LiCl. At the completion of training, CMCM produced a 69% reduction of saccharin consumption on drug trials, compared with 23% for conditioned controls. The stimulus properties of DMCM were then measured by its ability to reduce the preference for saccharin over water in a two-bottle choice test. DMCM reduced saccharin preference in rats that received discrimination training from 68% to 19%, but did not alter saccharin preference in conditioned controls. Other compounds with varying activity at BZ receptors were evaluated for their ability to substitute for the discriminative stimulus effects of DMCM. Two BZ receptor inverse agonists, beta-CCE (10-18 mg/kg) and FG 7142 (3.2-18 mg/kg), substituted completely for DMCM. Partial substitution for DMCM was shown by the BZ receptor antagonist CGS 8216 (3.2-10 mg/kg) and the non-BZ convulsant pentylenetetrazol (10-20 mg/kg). The BZ receptor agonists chlordiazepoxide (0.32-5.0 mg/kg), diazepam (0.32-10 mg/kg), and alprazolam (0.1-3.2 mg/kg) and the BZ receptor antagonist flumazenil (1.0-32 mg/kg) failed to substitute for the DMCM stimulus. Pretreatment with flumazenil (1.0 mg/kg) blocked the stimulus effects of the training dose of DMCM and produced a shift to the right of the DMCM generalization curve. The pattern of compounds that substituted for the DMCM stimulus and the blockade of that stimulus by flumazenil indicate that the stimulus properties of DMCM are associated with its effects as a BZ receptor inverse agonist.

Animals↗
PubMed1994

Selective breeding for negative contrast in consummatory behavior.

Rats showing either large or small reductions in licking following a shift from 32% to 4% sucrose were selectively bred for 7 generations. Rats from the 2 resulting lines reliably differed in successive negative contrast and in activity (radial-arm maze and open field). Differences in activity and contrast were not correlated. Heritability (h2) of the reaction to sucrose shift was reliable in the last 6 filial generations and equaled 0.64 in the F7 generation. The 2 lines did not differ (a) in response to the absolute rewarding value of sucrose or cocaine; (b) in open-field defecations or thigmotaxis; (c) in anticipatory contrast; or (d) in responsivity to midazolam. Responsivity to reward reduction may involve a relatively delimited psychological process that is amenable to selection.

Animals↗
PubMed1993

Conflicting evidence regarding the efficacy of ondansetron in benzodiazepine withdrawal.

These experiments tested the efficacy of the 5-hydroxytryptamine3 antagonist ondansetron (OND) in reversing various aspects of benzodiazepine withdrawal in rats. Three tests were used in which the benzodiazepine antagonist flumazenil was administered to rats receiving chronic administration of chlordiazepoxide. In one test, the elevated plus-maze, flumazenil produced a reduction in time spent in the open arms of the maze; OND completely reversed this effect of flumazenil in a dose-related fashion. However, OND failed to block the effects of the anxiogenic drug pentylenetetrazole (PTZ) in the elevated plus-maze. In a second test, rats were trained to discriminate PTZ. After chlordiazepoxide, flumazenil substituted for PTZ; OND failed to block flumazenil. In a third test, rats maintained on a chronic base line of chlordiazepoxide were trained to discriminate flumazenil from vehicle. In this discrimination, PTZ substituted for flumazenil, and pentobarbital blocked the flumazenil stimulus; OND, however, failed to block the flumazenil stimulus. In a separate set of experiments, OND also failed to reverse the suppression of responding produced in a conditioned emotional response paradigm. Thus, some data from the elevated plus-maze are consistent with the hypothesis that benzodiazepine withdrawal shares common effects with other stimuli known to be anxiogenic, and that OND blocks this aspect of withdrawal. However, all other data are inconsistent with the hypotheses that OND is anxiolytic or has efficacy in reversing benzodiazepine withdrawal. We suggest that ondansetron is likely to have minimal efficacy in humans for the treatment of sedative-hypnotic withdrawal.

Animals↗
PubMed1992

Discriminative stimulus properties of the benzodiazepine receptor antagonist flumazenil.

Rats were trained to discriminate the stimulus properties of the benzodiazepine (BZ) receptor antagonist flumazenil using a conditioned taste aversion procedure. On drug trials, fluid-restricted rats were injected with flumazenil (32 mg/kg), given access to a 0.25% saccharin solution for 30 min, and injected with LiCl (1.8 mEq/kg IP). On saline trials, injections of saline bracketed the period of saccharin consumption. Acquisition of the discriminated taste aversion, as measured by differential effects on drinking between saline and drug trials, developed after only five pairings of flumazenil with the LiCl injections. Flumazenil did not alter saccharin consumption in unconditioned controls (N = 9) that never received LiCl. The discrimination was also measured by flumazenil's ability to reduce the preference for saccharin over tap water using two-bottle choice tests. Flumazenil demonstrated dose-dependent generalization upon decreasing the training dose as low as 1 mg/kg. Two other BZ receptor antagonists of different chemical structure, CGS 8216 and ZK 93426, substituted completely for the flumazenil stimulus. Partial generalization was exhibited to the partial inverse agonists FG 7142 and beta-CCE, while the full inverse agonists DMCM and PTZ failed to substitute for the flumazenil stimulus. The BZ receptor agonists diazepam and alprazolam failed to substitute for the flumazenil stimulus, although partial generalization was shown with CDP. The results suggest that the BZ receptor antagonist flumazenil may produce intrinsic discriminative stimulus effects that are independent from those of BZ receptor agonists or inverse agonists.

Analysis of Variance↗
PubMed1992

Effect of chlorpromazine and haloperidol on negative contrast.

Rats shifted from 32 to 4% sucrose consume substantially less of the 4% solution than animals that have not had prior experience with the 32% sucrose. This negative contrast effect was not substantially influenced by chlorpromazine (1, 3, and 5 mg/kg) or haloperidol (0.1, 0.5, and 1.0 mg/kg). Haloperidol decreased overall lick frequency, but this decrease occurred proportionately in shifted and unshifted rats, leaving contrast intact. The benzodiazepine flurazepam (5, 10, and 20 mg/kg), included as a positive control, reduced contrast at the two highest doses. The results suggest that neuroleptics do not disrupt consummatory contrast and that dopaminergic antagonists may not influence reward relativity.

Animals↗
PubMed1991

Behavior of Maudsley reactive and nonreactive rats (Rattus norvegicus) in three consummatory contrast paradigms.

Maudsley reactive (MR/Har) and nonreactive (MNRA/Har) rats (Rattus norvegicus) were tested in successive, simultaneous, and anticipatory contrast procedures. The MR/Har rats showed smaller successive negative contrast effects than the MNRA/Har rats when shifted from 32% to 4% sucrose, and the degree of contrast was smaller in animals of both strains than that typically obtained with unselected Sprague-Dawley derived rats. Chlordiazepoxide (4 and 8 mg/kg), which typically reduces contrast, did not influence degree of contrast in rats of either strain. Animals of both strains showed positive and negative contrast in the simultaneous contrast procedure, but degree of contrast in both cases was smaller in rats of the MR/Har strain. Animals of both strains also showed anticipatory contrast when a 0.15% saccharin solution preceded 32% sucrose in once-per-day pairings. In terms of latency to initiate licking, the MNRA/Har rats showed a contrast effect, but the MR/Har rats showed a "reinforcement" effect--shorter latency when saccharin preceded sucrose than when saccharin preceded saccharin. Open-field tests showed typical strain differences: The MNRA/Har rats ambulated more, reared more, defecated less, and showed less thigmotaxis than the MR/Har rats.

Animals↗
PubMed1990

Effect of serotonergic drugs on negative contrast in consummatory behavior.

The effect of acute and chronic administration of the 5-HT1A agonist buspirone on successive negative contrast was investigated in Experiments 1-6. Contrast in consummatory behavior was induced by shifting rats from a 32% to a 4% sucrose solution. Experiments 1-5 showed that buspirone (0.125, 0.25, 0.5, 1.0, 2.0, 15.0 mg/kg) was ineffective in alleviating contrast or in facilitating recovery from contrast. The 15 mg/kg dose substantially decreased consummatory responding. Experiment 6 showed that the chronic (24 days) administration of buspirone (0.5, 2.0 mg/kg) also did not alleviate contrast. The chronic, but not the acute administration of the 2.0 mg/kg dose decreased consummatory behavior. In Experiment 7 the 5-HT1A agonist gepirone (2.5, 5.0 and 10.0 mg/kg) was also found to be ineffective in reducing contrast but, at the higher doses, decreased overall sucrose intake. Experiments 8 and 9 found that the 5-HT2 antagonists ketanserin (2.0 and 8.0 mg/kg) and ritanserin (0.63 and 2.5 mg/kg) also did not alleviate contrast. Midazolam (1.0 mg/kg), included as a positive control, eliminated contrast. These data suggest that serotonergic mechanisms are not involved in negative contrast.

Animals↗
PubMed1989

Rats (Rattus norvegicus) selectively bred to differ in avoidance behavior also differ in response to novelty stress, in glycemic conditioning, and in reward contrast.

The behavior of the Syracuse high avoidance (SHA) and Syracuse low avoidance (SLA) rats, selectively bred by Brush (F. R. Brush, J. C. Froehlich, & P. Sakellaris, 1979, Behavior Genetics, 9, 309-316) to differ in avoidance behavior, was examined in several different tasks. The SLA rats showed a greater elevation in plasma glucose when exposed to a novel environment; after 7 days of exposure to this environment there was evidence of habituation in the SHA rats but not in the SLA rats; the SHA rats showed a hyperglycemic conditioned response in a glycemic conditioning procedure, the SLA rats showed no evidence of conditioning but had higher overall levels of plasma glucose; both strains showed reliable successive negative contrast effects in consummatory behavior when shifted from 32 to 4% sucrose, but the contrast was larger in the SLA rats; the administration of chlordiazepoxide eliminated negative contrast in the SLA rats but had no effect on contrast in the SHA rats; and the SLA rats were reliably heavier than the SHA rats. The behavioral differences were considered in the context of differences in emotional reactivity between the two strains.

Animals↗
PubMed1989

Effects of intrahippocampal administration of colchicine on incentive contrast and on radial maze performance.

The behavior of rats given intradentate injections of the neurotoxin colchicine was examined in three experimental settings. In Experiment 1, colchicine-treated, artificial cerebrospinal fluid (CSF)-treated, and untreated animals did not differ in the intake of 32% and 4% sucrose solutions, nor did they differ in degree of successive negative contrast when the 32% solution was changed to 4% sucrose. In Experiment 2, the colchicine-treated and CSF-treated animals did not differ in degree of suppression in the intake of a 0.15% saccharin solution when it preceded 32% sucrose in once-daily pairings (anticipatory contrast), nor did they differ in reversal performance when saccharin-sucrose and saccharin-saccharin pairings were reversed. In Experiment 3, the colchicine-treated animals were substantially impaired in radial-arm maze performance compared with CSF-treated controls. These results suggest that a completely functioning hippocampus is not necessary for the memory of reward quality, the comparison of rewards, the suppression of behavior when reward is decreased, the formation of associations between two levels of reward, and the reversal of this association, as long as these processes are reflected in consummatory behavior. The data are interpreted in terms of differences between instrumental behavior and sensory memory and/or consummatory behavior--an interpretation that is not incompatible with a deficiency in working memory in the animals with lesions.

Animals↗
PubMed1989

Negative contrast in the consumption of sucrose and quinine adulterated sucrose solutions.

Rats shifted from a 40% sucrose solution to a quinine-adulterated (30 mg/100 ml) 40% sucrose solution showed a reduction in consumption to a level considerably below that of animals exposed to only the quinine-adulterated solution. The animals tended to recover from this negative contrast effect over a 5-day postshift period and, in general, the degree of contrast was about equivalent to that of animals shifted from a 32% to a 4% sucrose solution. There were no sex differences in the rats shifted from 32% to 4% sucrose, but female rats shifted to the quinine-adulterated sucrose showed larger contrast effects than male rats exposed to the same shift.

Animals↗
PubMed1987

The effects of morphine in the consummatory contrast paradigm.

Rats shifted from 32% to 4% sucrose show a negative contrast effect, licking significantly less than animals that receive only 4% sucrose. The effects of morphine sulfate (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/kg) on negative contrast were investigated in four experiments. Contrast was reduced on both the 1st and 2nd postshift day by the 4.0 and 8.0 mg/kg doses, but the effects were less robust than those seen with the benzodiazepines. The effects of morphine on contrast were dissociable from simple increases in sucrose consumption. Naloxone (0.25, 0.5, and 1.0 mg/kg) had no effect on contrast or sucrose intake. However, the contrast-reducing effect of morphine (4.0 mg/kg) was blocked by pretreatment with naloxone (0.50 mg/kg). The results are discussed in terms of other anxiolytic screening paradigms that have obtained "partial anxiolytic effects" using morphine.

Animals↗
PubMed1986

Corticosterone, novelty-induced hyperglycemia, and chlordiazepoxide.

Rats moved to novel environments for a 20 minute period showed increased plasma corticosterone levels--the greater the difference between the housing context and the novel environment, the greater the increase in corticosterone. Plasma glucose levels (PGL) also increased with increasing environmental novelty and these PGL changes were moderated by pretreatment with chlordiazepoxide (10 mg/kg). The increases in corticosterone and PGL were greater in a context previously shown to lead to hyperglycemic conditioning following insulin administration than in a context previously shown to lead to hypoglycemic conditioning. These results imply that the directionality of glycemic conditioning may be related to the initial stressfulness of the conditioning environment.

Animals↗
PubMed1986

Successive, simultaneous, and anticipatory contrast in the consumption of saccharin solutions.

Contrast effects were obtained in rats in the consumption of saccharin solutions in three different paradigms. Degree of negative contrast varied as a function of concentration disparity, but not equally in the three procedures. Successive negative contrast occurred following shifts from 0.15% to either 0.075% or 0.05% saccharin but did not occur following shifts to 0.10% or 0.125% saccharin. Some degree of simultaneous contrast was obtained with all four concentration disparities. Anticipatory contrast, where the intake of the first substance is suppressed by a more preferred second substance, occurred only in the case of the 0.05%-0.15% difference in concentrations. It was suggested that the several contrast paradigms engage somewhat different psychological processes differentially involving emotional, sensory, and associative mechanisms, but all lead to behavior based on relative value. A modification of Toates's (1981) incentive model of ingestive behavior was suggested to incorporate relativity effects based on both associative and nonassociative factors in the consumption of both nutritive and nonnutritive substances.

Animals↗
PubMed1984

Effects of chlordiazepoxide on novelty-induced hyperglycemia and on conditioned hyperglycemia.

Moving rats from their home cages to a different environment for a twenty minute period tended to raise plasma glucose levels (PGLs). In general, the more different the novel environment was from the housing condition, the greater the rise in PGL. Stimulus contexts that have led to conditioned hyperglycemia in previous experiments caused a larger rise in PGLs than stimulus contexts that led to conditioned hypoglycemia in previous experiments. These glycemic effects of environmental novelty did not habituate across seven exposure periods. Experiment 2 showed that chlordiazepoxide (CDP) reduced PGLs in animals transported to novel environments. Experiment 2 also showed that conditioned hyperglycemia occurred when insulin was administered in the environment that led to the highest PGLs in Experiment 1, and that conditioned hypoglycemia occurred in this same environment when the animals were regularly pretreated with CDP. Administering insulin in an environment that did not initially elicit a large rise in PGL resulted in a tendency towards conditioned hypoglycemia that was not influenced by CDP.

Animals↗