ECT, dopamine and delusions.
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Delusions↗
Biomedical subjects
S J Cooper
Publications and source records attributed to S J Cooper.
beta-Phenylethylamine-, d-amphetamine-and l-amphetamine-induced place preference conditioning in rats.
The conditioned place preference paradigm was used to study the reinforcing properties of beta-phenylethylamine (PEA), d-amphetamine and l-amphetamine. The results confirmed that each drug produced place preferences for a distinctive environment that had previously been paired with the drug treatment. PEA proved as effective as the amphetamine isomers, although substantially less potent. This is the first report of a reinforcing effect of PEA in the rat and supplements previous evidence that PEA is self-administered intravenously in the dog.
Amphetamine↗
Effects of chlordiazepoxide on drinking compared in rats challenged with hypertonic saline, isoproterenol or polyethylene glycol.
Several investigators have shown that anxiolytic benzodiazepines stimulate additional water consumption in rats made thirsty by water deprivation. The present report extends this work by showing that chlordiazepoxide (CDP) enhanced drinking in rats challenged with either cellular or extracellular dehydration, following hypertonic saline or polyethylene glycol injection respectively. Since CDP also increased drinking in control animals, it may have produced a direct dipsogenic effect which acted additively with respect to the physiological thirst challenges. In contrast, CDP did not enhance water intake during the dipsogenic action of the beta-adrenergic agonist, isoproterenol. The data provide new evidence that benzodiazepine mechanisms may be involved in thirst and the controls of drinking.
Animals↗
Minireview. Benzodiazepine-opiate antagonist interactions in relation to feeding and drinking behavior.
Benzodiazepines reliably produce overconsumption of food and fluids. Opiate antagonists, naloxone and naltrexone, block the benzodiazepine-induced hyperphagia and hyperdipsia at low doses. Hence, activation of endogenous opioid mechanisms may be closely involved in the benzodiazepine facilitatory effects on ingestional behavior. Evidence is reviewed that opiate antagonists diminish feeding and drinking responses, and may enhance satiety processes in feeding and drinking, in addition to selectively diminishing the palatability of attractive foods and fluids. It is proposed that a single mechanism of action of the opiate antagonists would be sufficient to account for both effects on feeding and drinking. Biochemical data confirm that acute benzodiazepine treatment in vivo is associated with a naloxone-reversible release of striatal enkephalin. It is possible therefore that there is a close association between the behavioral and biochemical data, which both show that acute benzodiazepine effects are reversed by opiate antagonists. The implied relationship between benzodiazepine and endogenous opioid mechanisms may be relevant to the question of concurrent opiate-benzodiazepine abuse.
Animals↗
Effects of naloxone and naltrexone on the increased water intake and drinking duration in phenobarbitone-treated rats.
In two experiments, phenobarbitone sodium (30 mg/kg) reliably enhanced water consumption and extended the duration of drinking in 24h water-deprived male rats. The opiate receptor antagonists naloxone (0.1-10 mg/kg) and naltrexone (0.1-10 mg/kg) both decreased water intake and reduced the duration of drinking. When the barbiturate was given in conjunction with either naloxone or naltrexone, phenobarbitone and the opiate antagonist exerted opposite effects on the two measures of drinking. While it was true that both opiate antagonists reduced water intake and drinking duration in barbiturate-treated animals, the barbiturate-induced enhancement of drinking was in no way modified by concurrent opiate antagonist treatment. Hence, the effects of phenobarbitone and of the two opiate antagonists upon the drinking measures appeared to be quite independent. There was no evidence, therefore, that the effects of phenobarbitone upon drinking were related to endogenous opioid mechanisms. The possible contrast between benzodiazepine- and barbiturate-induced hyperdipsia is briefly considered in the light of these results.
Animals↗
Effects of naloxone and its quaternary analogue on fluid consumption in water-deprived rats.
The effects of subcutaneous administration of naloxone and its quaternary analogue on the consumption of water, saline and saccharin solution were investigated in the water-deprived rat. Quaternary naloxone (0.01-10 mg . kg-1), effective in blocking peripheral opiate receptors, had no effect on fluid intake. In contrast, naloxone (0.01-10 mg . kg-1), produced dose-dependent attenuation of intake for each of the three fluids, indicating a central location of the relevant opiate receptors. Access to saline induced additional drinking, compared with water intake, due to an extension of the initial avid consumption which follows the period of water-deprivation. This enhancement of drinking was blocked by naloxone, but not by its quaternary analogue. Interactions between naloxone and taste factors in drinking may, therefore, depend on blockade of central opiate receptors.
Animals↗
Benzodiazepine-opiate antagonist interactions and reward processes: implications for drug dependency.
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Animals↗
Effects of opiate agonists and antagonists on fluid intake and saccharin choice in the rat.
Both naloxone (3 and 10 mg X kg-1) and naltrexone (1-10 mg X kg-1) abolished the preference for a highly palatable 0.05% sodium saccharin solution in rats that had been adapted to a 22 hr water-deprivation schedule. The effect occurred as a result of a selective decrease in the consumption of the saccharin solution, since the intake of water, which was concurrently available in the two-fluid choice test, remained unaffected. When a less preferred saccharin solution was used (0.01%), naltrexone exerted a similar suppressant effect on the sodium preference, whilst naloxone failed to produce significant effects on the intake of saccharin solution or water. The data for the opiate agonists were interpreted in terms of a drug-induced blockade of the natural reward of highly palatable fluids in thirsty rats. In the same choice test, morphine and a stabilised enkephalin analogue, with a selective agonist action at mu-opiate receptors (RX783030), failed to influence the preference for the palatable saccharin solutions. In water-deprived animals, at least, exogenous opiate agonists, active at mu-receptors, did not appear to influence the reward of the palatable solutions.
Animals↗
Suppression of saccharin-induced drinking in the nondeprived rat by low dose diazepam treatment.
Access to a highly palatable 0.005 M sodium saccharin solution resulted in considerable overdrinking in nondeprived rats over a 6 hr observation period. Contrary to previous reports documenting benzodiazepine-induced hyperdipsia in animals challenged with thirst stimuli or in animals exhibiting schedule-induced drinking, diazepam (0.1-3.0 mg/kg) had no effect to enhance the intake of the saccharin solution. Instead, diazepam produced a significant suppression of fluid consumption, in a manner not monotonically related to dose. Thus, diazepam (0.3 mg/kg) produced maximal suppression which did not dissipate over a 6 hr period, while diazepam (3.0 mg/kg) had no effect. Possible behavioral mechanisms by which low dose diazepam treatment might reduce the drinking are briefly considered.
Animals↗
Patterns of drinking in the rat following the administration of opiate antagonists.
Durations of drinking were recorded for water-deprived rats as they drank to satiety, following SC injections of naloxone (0.1-10.0 mg/kg), naltrexone (0.1-10.0 mg/kg) or saline vehicle. The results provided evidence for the effects of opiate antagonists on the temporal pattern of drinking exhibited by water-deprived animals. A separate, time-sampling procedure was used to supplement the drinking duration data, and showed that the opiate antagonists may suppress water consumption during a period 2.5-7.5 min after the start of the initial drinking bout. A second experiment confirmed that the pattern of drinking displayed during schedule-induced polydipsia in the rat is resistant to any suppressant effect of a moderate dose of an opiate antagonist. The similarity between opiate receptor blockade and water preloading in their effect on drinking in response to water deprivation, and lack of effect on schedule-induced polydipsia is discussed. Opiate antagonists may affect drinking principally by imposing a thirst satiety signal.
Animals↗
GABA and endorphin mechanisms in relation to the effects of benzodiazepines on feeding and drinking.
Behavioural actions of benzodiazepines have a number of significant characteristics. Anxiolytic effects are demonstrable both clinically and experimentally; in addition, there is excellent evidence for a reinforcing effect of these compounds, and a direct involvement in ingestional responses. This review focusses on the effects of benzodiazepines on the latter feeding and drinking responses. A necessary mediator of benzodiazepine action in the central nervous system appears to be the facilitation of inhibitory GABAergic neurotransmission. It follows, therefore, that behavioural consequences of benzodiazepine action may depend crucially on enhanced GABAergic activity in the brain. Evidence for some involvement of GABAergic mechanisms in the control of feeding and drinking responses is reviewed. Only a few data are so far available to link benzodiazepines effects on ingestional behaviour directly to GABAergic transmission. A major current theme in the psychopharmacology of feeding and drinking behaviour is the possible involvement of endogenous opioid peptides. There is a strong suggestion in the experimental data that there are links between benzodiazepine and endorphinergic mechanisms in relation to ingestional responses. A promising future line of approach appears to be a delineation of benzodiazepine-GABA-endorphin interrelations in the control of food and water consumption.
Animals↗
Pharmacology of beta-phenylethylamine-induced seizures in mice.
The endogenous trace amine beta-phenylethylamine (PE) produced tonic-clonic seizures in male Swiss mice when administered in doses of 125-200 mg/kg. The number of mice exhibiting PE-induced seizures, the latency to onset of first seizure and the latency to loss of the righting reflex were dose dependent. Pretreatment with the benzodiazepines diazepam, chlordiazepoxide, midazolam and clonazepam significantly reduced the incidence of PE-induced seizures. Similarly, increasing brain gamma-aminobutyric acid (GABA) levels by injection of the GABA-transaminase inhibitors aminooxyacetic acid or gabaculine afforded significant protection against PEA's convulsant effects. The data suggest that PE when administered at high doses may interfere either directly or indirectly with GABAergic neurotransmission in the central nervous system. In addition, since PE induces an epileptiform spiking pattern and produces seizures in rodents it appears possible that the amine may play a role in some forms of human epilepsy.
Animals↗
Fluid consumption in water-deprived rats after administration of naloxone or quaternary naloxone.
Water-deprived male rats were given access to water, or to a 0.005M sodium saccharin solution, or to a 0.9% sodium chloride solution, during a 30 min test period. Naloxone (0.01-10.0 mg/kg) produced dose-dependent reductions in the consumption of each fluid. Saccharin-drinking was significantly reduced by 0.01 mg/kg naloxone, and water- and saline-drinking by 0.1 mg/kg naloxone. Quaternary naloxone (0.01-10.0 mg/kg) had no effect on drinking under any condition. Access to the saline solution resulted in hyperdipsia, due to a prolongation of the initial bout of avid drinking in the thirsty rats. Naloxone, in small doses, completely abolished this hyperdipsia. Since the quaternary compound had no effect, it was concluded that opiate antagonist suppression of saline-induced hyperdipsia was probably mediated at central opiate receptors.
Animals↗
The effect of propranolol on CSF amine metabolites in psychiatric patients.
In view of the central side effects of beta-adrenoceptor blocking agents and their alleged antipsychotic action in the absence of DA receptor blockade, it is important to establish which neurotransmitters are likely to be involved. Previous animal and patient studies have, however, produced conflicting data on this point. The changes in CSF HVA, 5HIAA and MHPG during treatment with propranolol (960 mg/day) in chronic schizophrenic patients were monitored on four occasions over 30 days. Clinical changes were monitored by the Wing and Krawiecka Scales and motor activity was assessed by pedometer. CSF HVA levels were significantly increased by propranolol and the rise continued throughout the 30 day period. There were no significant changes in the other metabolites. There was no evidence of any therapeutic benefit from propranolol treatment in these patients. These findings may explain the central side-effects and occasional reports of schizophreniform psychosis after propranolol, since an increase in DA turnover occurs without DA receptor blockade.
Adult↗
Aggressive behaviour in a psychiatric observation ward.
Episodes of aggression were monitored, using a questionnaire, for a 6-month period in the female observation ward of a General Psychiatric Hospital. The results show that: a small group of schizophrenic patients were responsible for most of the incidents; nursing staff and other patients fell victim equally frequently; few of the incidents were predictable. Psychotic symptoms appear to be the main cause. More effective treatment of some persistently psychotic, apparently neuroleptic-resistant, aggressive patients should reduce the prevalence of violent behaviour. Drug-free observation periods in more recently admitted patients, or patients involved in pharmacological studies, however, were not associated with violent incidents.
Aggression↗
Specific benzodiazepine antagonist RO15-1788 and thirst-induced drinking in the rat.
Midazolam, a new water-soluble benzodiazepine, increased the water intake of water deprived rats. The effect was abolished by concurrent treatment with the benzodiazepine antagonist, RO15-1788. The lack of effect of RO15-1788 on phenobarbitone-induced hyperdipsia confirmed the specificity of the antagonist action. Alone RO15-1788 (0.3-30 mg . kg-1) had no effect on thirst-induced drinking. Thus, it was not necessary to posit the action of an endogenous benzodiazepine ligand in thirst-induced drinking.
Animals↗
Benzodiazepine mechanisms and drinking in the water-deprived rat.
Benzodiazepines (diazepam, midazolam, flurazepam and chlordiazepoxide) produced a hyperdipsia in rats which were well-adapted to a daily 22 hr water-deprivation schedule. The hyperdipsia occurred as a result of extensions in the time-course of drinking without impairment in the efficiency of drinking (rate of water intake). At doses larger than those associated with hyperdipsia, the rate of water consumption was markedly impaired, so that any extension in the duration of drinking was offset by the impaired efficiency. As a result, a non-monotonic relationship between dose of benzodiazepine and volume of water intake could be generated. The convulsant benzodiazepine, Ro5-3663, produced a reduction in drinking, at sub-convulsant doses and without general motor interference. This hypodipsia was completely reversed by concurrent treatment with either diazepam or midazolam. The results are discussed in terms of possible behavioural and biochemical mechanisms which may underlie benzodiazepine-induced hyperdipsia.
Animals↗
Effects of opiate antagonists and of morphine on chlordiazepoxide-induced hyperdipsia in the water-deprived rat.
The effects of naloxone hydrochloride (0.01-10 mg X kg-1), naltrexone hydrochloride (0.01-10 mg X kg-1), and morphine sulphate (0.01-10 mg X kg-1) on the increased water consumption provoked by administration of chlordiazepoxide (10 mg X kg-1) were investigated in male rats which had been adapted to a 22 hr water-deprivation schedule. As previously reported, both naloxone and naltrexone dose-relatedly reduced water ingestion. Naloxone at 1 mg X kg-1 and naltrexone at 0.1 mg X kg-1 completely blocked the chlordiazepoxide-induced hyperdipsia. Since both opiate antagonists removed the chlordiazepoxide-induced effects in small doses, their effect can plausibly be attributed to opiate receptor blockade. Hence, chlordiazepoxide-induced hyperdipsia may depend upon the activation of endogenous opioid mechanisms. Morphine had little effect on drinking, unless a large dose (10 mg X kg-1) was used, when the thirst-induced and chlordiazepoxide-induced drinking were attenuated. The data provided no evidence that morphine, a mu opiate agonist, enhanced chlordiazepoxide-induced water consumption. The results are considered in relation to other relevant behavioural and biochemical findings.
Analysis of Variance↗