A benzodiazepine agonist and contragonist have hypothermic effects in rodents

Taylor, Stuart C.; Hj, Little; Nutt, David; Sellars, N.

doi:10.1016/0028-3908(85)90097-8

Cited by 50 publications

(12 citation statements)

References 15 publications

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“…This suggests that the physiological response to this "pharmacological stressor" is in some ways very different to that provoked by other more conventional forms of stress. The lowered EE seen with FG-7142 may in part be a reflection of the tendency towards lowered locomotor activity with this treatment, an effect that has been reported in other studies (Taylor et al 1985;Jaskiw and Weinberger 1990). In addition, previous studies have shown that FG-7142 induces hypothermia (Taylor et al 1985;Jackson and Nutt 1991), suggesting that inhibition of basal metabolism may result from administration of this drug.…”

Section: Discussionmentioning

confidence: 79%

“…The lowered EE seen with FG-7142 may in part be a reflection of the tendency towards lowered locomotor activity with this treatment, an effect that has been reported in other studies (Taylor et al 1985;Jaskiw and Weinberger 1990). In addition, previous studies have shown that FG-7142 induces hypothermia (Taylor et al 1985;Jackson and Nutt 1991), suggesting that inhibition of basal metabolism may result from administration of this drug. The relatively small sample size used in experiment 3 precludes any definite conclusions being made regarding this issue at present.…”

Section: Discussionmentioning

confidence: 79%

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Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam

1994

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Changes in O2 consumption, CO2 production and locomotor activity were examined in rats exposed to (1) brief footshock, (2) an aversive conditioned stimulus (CS) predicting footshock, or (3) the anxiogenic drug FG-7142. Respiratory quotient (RQ = CO2 produced/O2 consumed) and energy expenditure [EE = O2 consumed (364 + 113RQ)] were derived to give an estimate of the energy substrate (fat, carbohydrate or protein) being utilised and total substrate oxidation respectively. In experiment 1, footshock (4 x 5 s 0.6 mA shocks over 2 min) produced an immediate increase in RQ, EE and activity. The RQ and EE effects were attenuated by the benzodiazepine midazolam (1 mg/kg). In experiment 2, an aversive CS, consisting of flashing light and buzzer that had 24 h earlier been repeatedly paired with foot-shock (20 x 5 s 0.6 mA shocks) caused a pronounced drop in RQ, an increase in EE and locomotor activity suppression. The effects of the aversive CS on RQ and EE were reversed by midazolam (1 mg/kg). In experiment 3, FG-7142 (10 mg/kg) produced a steep drop in RQ that persisted for at least 2 h and which was reversed by midazolam (1 mg/kg) and delayed by the benzodiazepine antagonist RO 15-1788 (10 mg/kg). FG-7142 also tended to inhibit EE and locomotor activity, but these effects did not reach statistical significance. Overall, these data show that stress causes profound alterations in RQ, EE and activity and that the pattern of change in these parameters differs with the nature of the stressor involved.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 79%

Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam

1994

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“…However, it is possible that FG 7142 was potentiating an anticonvulsant effect of Ro 15-1788, which when using the PTZ infusion method is normally only seen at high doses of Ro 15-1788 (Nutt et al, 1982a). The unusual shape of the dose-response curve for the proconvulsant effects of FG 7142 appears to be due to a phenomenon peculiar to the convulsion threshold as we have also measured the effects of FG 7142 on body temperature and with this parameter, the highest doses of the compound did cause greater changes than the lower doses (Taylor et al, 1984).…”

Section: Chronic Treatmentmentioning

confidence: 81%

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

Little

Nutt

Taylor

1984

British J Pharmacology

133

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The effects of the acute and chronic administration of the ,B-carboline benzodiazepine receptor ligand, FG 7142 were studied in mice. 2 On acute administration FG7142 (at doses between 10 and 40mgkg-1) lowered seizure thresholds to infused pentylenetetrazol (PITZ) but showed an unusual dose-response curve in that higher doses had less effect. The duration of action was considerably longer than that of other 1-carbolines, such as ethyl-1-carboline-3-carboxylate (ICCE). 3 During repeated administration, doses of FG 7142 which were initially proconvulsant subsequently produced generalized seizures on average in 60% of animals after 12 once daily treatments. This seemed to be a form of chemical kindling. 4 The effects of different drug administration regimes were studied. Once daily dosage was shown to be the optimum for kindling production, and was therefore used for subsequent experiments. 5 Kindling lasted for at least one month after 12 single once daily doses of 40mg kg-(FG 7142). 6 The administration of the benzodiazepine antagonist Ro 15-1788 concurrent with FG 7142 prevented kindling. When Ro 15-1788 was given to kindled animals along with a challenge dose of FG 7142, it prevented the expression of kindled seizures. These data show that kindling is mediated via the benzodiazepine receptor.

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“…Measurements of body temperature were made by rectal probe inserted 2 cm, connected to a thermometer. As the body temperatures of mice are very labile, an experimental schedule was used which was designed to demonstrate most clearly the effects of the drugs (Taylor et al 1985). For every experiment the controls and test animals were measured concurrently.…”

Section: Acute Effectsmentioning

confidence: 99%

Changes in benzodiazepine/GABA receptor complex function in benzodiazepine-tolerant mice

et al. 1988

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Mice were given flurazepam, 40 mg k-1, IP, once daily for 7 consecutive days. Twenty-four and forty-eight hours after the last injection measurements were made of the effects on convulsion threshold, body temperature and locomotor activity, of drugs acting on the GABA receptor complex. Significant decreases were seen in the hypothermic and hypomobility effects of progabide at 48 h, but no significant changes were seen in the effects of pentylenetetrazol or pentobarbitone. The actions of picrotoxin in all three types of test and the convulsant action of bicuculline (IP) were significantly decreased at 24 h but not at 48 h. The convulsive, but not the hypothermic, effects of picrotoxin were increased at the 48 h interval. These results may suggest that the chronic benzodiazepine treatment decreased some aspects of GABA receptor function at 48 h after the last dose; however, such an effect probably does not explain the previously reported increases in the effects of inverse agonists following chronic agonist treatment.

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A benzodiazepine agonist and contragonist have hypothermic effects in rodents

Cited by 50 publications

References 15 publications

Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam

Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam

Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling

Changes in benzodiazepine/GABA receptor complex function in benzodiazepine-tolerant mice

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