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Biomedical subjects

G E Hunt

Publications and source records attributed to G E Hunt.

At least 55 records · Page 3Linked to original sources
PubMed1984

Studies of rat brain metabolism using proton nuclear magnetic resonance: spectral assignments and monitoring of prolidase, acetylcholinesterase, and glutaminase.

The first application of inversion-recovery spin-echo proton nuclear magnetic resonance spectroscopy to the monitoring of reactions in rat brain preparations is presented. The initial report of the assignment of proton spin-echo nuclear magnetic resonance spectra from rabbit brain homogenates (C. R. Middlehurst et al., J. Neurochem. 42, 878-879, 1984) was used to assist in the assignment of spectra acquired from rat brain homogenates that were obtained from animals killed by cervical fracture or focussed microwave irradiation. Microwave-irradiated brains were divided into four major anatomical regions. Differences in metabolite levels were detected when spectra from fresh tissue and from various regions were compared. The in situ steady-state kinetics of prolidase in whole brain homogenate was determined. The procedure relies on the spectral differences between enzyme substrates and reaction products. The concentration dependence of the rate of hydrolysis of glycyl-L-proline was discribable by the Michaelis-Menten expression with a Michaelis constant of 1.90 mmol L-1 and a maximal velocity of 9.30 mumol min-1 mg-1 protein. The reactions catalysed by glutaminase and acetylcholinesterase in the brain were also monitored.

Acetylcholine↗
PubMed1983

Dissociating the determinants of self-stimulation.

Four experiments were conducted to elucidate the determinants of the initiation of and escape from electrical stimulation of the lateral hypothalamus under several different reinforcement schedules. The first experiment of this series used correlational and factor analytic techniques to show that, under continuous reinforcement, the vigour of initiation is determined more by forcement than by positive reinforcement. Forcement is defined as all of the performance changes directly elicited and potentiated by the stimulation. Escape is determined by adaptation of positive reinforcement, not by negative reinforcement or aversion. Continuous reinforcement schedules are, therefore, not appropriate for studying either the positive or negative reinforcement produced by brain stimulation. The second experiment used fixed-interval reinforcement schedules to eliminate the effects of forcement on initiation and adaptation of positive reinforcement on escape. Parametric manipulations indicate that activity in the positive reinforcement and escape systems is a simple function of stimulation charge. The combination of parameters which make up a given charge is of relatively little importance. However, the positive reinforcement system becomes maximally activated at far lower charges than does the escape system. The third experiment used a T-maze technique to show that, after 5 sec, anterior hypothalamic stimulation becomes negatively reinforcing, but posterior hypothalamic stimulation does not. Since the escape from posterior hypothalamic stimulation on a fixed-interval schedule can be dissociated from both negative reinforcement and adaptation of positive reinforcement, it is suggested that such escape is reinforced by a positive process triggered by the offset of stimulation (OFF positive reinforcement). The fourth experiment showed that stimulation trains longer than 10 sec are significantly less positively reinforcing than much shorter trains. This reduction in positive reinforcement confirms the development of negative reinforcement in long trains of hypothalamic stimulation, even at posterior electrodes. Negative reinforcement appears to be as general a property of hypothalamic stimulation as is positive reinforcement. Thus, depending on the reinforcement schedule and electrode site, the initiation of lateral hypothalamic stimulation may be determined by ON positive reinforcement, OFF positive reinforcement and forcement. Escape may be determined by OFF positive reinforcement, adaptation of positive reinforcement and negative reinforcement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Energy balance and hypothalamic self-stimulation.

The effects of negative energy balance on self-stimulation are a matter of considerable disagreement. This disagreement undoubtedly reflects the inadequacies of the continuous reinforcement self-stimulation procedures used in this type of experimentation. The present experiment uses a new fixed-interval reinforcement shuttle-box procedure which provides indices of reward and stimulation escape that are free from the numerous performance altering effects that confound continuous reinforcement performance. Whereas 24 h of food deprivation had no effect on stimulation initiation or escape rates, 48 h of food deprivation selectively increased initiation rates. The enhancement of reward was seen over virtually the entire anterior-posterior extent of the lateral hypothalamus and occurred irrespective of the occurrence of any stimulus-bound behaviors. Thus negative energy balance appears to selectively increase the excitability of reward-related neurons in the lateral hypothalamus. The self-stimulating rats became clearly hyperphagic, yet their weight gains were not significantly different from those of controls. The self-stimulation must, therefore, have greatly increased energy expenditure. Thus, not only does energy balance affect self-stimulation, but self-stimulation appears to affect energy balance.

Animals↗
PubMed1982

Pharmacokinetics of standard (lithicarb) and sustained-release (Priadel) lithium carbonate preparations in patients.

Equivalent oral dosages (800 mg, 21.6 mmol) of a standard (Lithicarb) and a sustained-release (Priadel) lithium carbonate preparation were administered to six patients receiving lithium maintenance treatment using a randomized cross-over design. There were no significant differences in the two preparations for 24 hour plasma level curves, 24 hour bioavailability, peak plasma concentrations (Cmax), time to peak plasma concentrations (Tmax) or urinary excretion rates. These results are in agreement with a previous study using Priadel in healthy volunteers, and indicate that Priadel is a delayed-release, rather than a true sustained-release preparation. In order to maintain therapeutic plasma levels and to minimise adverse effects that may occur with high plasma lithium levels, Priadel needs to be administered in divided dosages rather than as a single daily dose.

Administration, Oral↗
PubMed1981

The tetracyclic antidepressant mianserin: evaluation of its blockade of presynaptic alpha-adrenoceptors in a self-stimulation model using clonidine.

It has been suggested that the tetracyclic antidepressant mianserin may be an antagonist at inhibitory presynaptic alpha-adrenoceptors. If mianserin exerted a selective antagonist effect it should produce effects that are essentially opposite to those of a selective agonist such as clonidine. This hypothesis was investigated in a shuttle-box self-stimulation model previously shown to be sensitive to alpha-adrenergic drugs. In this model a presynaptic alpha-adrenoceptor antagonist would be expected to enhance self-stimulation and to reverse the inhibitory effects of clonidine. Mianserin (2.5-4.0 mg/kg) did not enhance self-stimulation, but instead produced a selective inhibition of reward. Further, mianserin did not reverse the inhibitory effects of clonidine on self-stimulation. These data suggest that if mianserin is an antagonist of the presynaptic alpha-adrenoceptors it is not a selective antagonist. It is possible that the presynaptic alpha-adrenoceptor antagonism may be effects on postsynaptic alpha-adrenoceptors and/or on a presynaptic noradrenaline reuptake mechanism.

Adrenergic alpha-Antagonists↗
PubMed1981

A linkage study of manic-depressive disorder with HLA antigens, blood groups, serum proteins and red cell enzymes.

Families with a two-generational history of affective disorder and well and ill sibs were selected from a population of bipolar manic-depressive patients and typed for HLA antigens, blood groups, serum proteins and red cell enzymes. Segregation of specific HLA alleles was not associated with affective illness across family pedigrees. Further, no significant associations were found between affective disorder and ABO, Rh, MNSs blood groups or Hp, EsD, C3, Gc or PGM. Using the lod score method of Morton (1955) for determining linkage, these data indicated that close linkage is unlikely for affective disorder and HLA alleles, haptoglobin, Rh factor, or ABO blood groups.

Adolescent↗
PubMed1981

Assessment of tardive dyskinesia in psychiatric outpatients using a standardized rating scale.

Psychiatric outpatients were assessed for dyskinetic movements using the abnormal involuntary movement scale (AIMS). The prevalence of tardive dyskinesia in an Australian sample of 66 patients was 44% which is similar to reported prevalence in other countries. Although the prevalence was significantly higher in patients over 45 years of age and with more than a 5 year history of neuroleptic medication, there were no significant correlations between presence of dyskinesias and age, sex or duration of neuroleptic treatment. Organic factors such as neurological disorders, ECT or alcoholism were not related to dyskinetic movements, nor was the use of anticholinergic or tricyclic antidepressant medication. The AIMS is a reliable rating scale for dyskinetic movements and could be used more widely as a screening instrument for early detection of tardive dyskinesia.

Adolescent↗
PubMed1980

Apomorphine: selective inhibition of the aversive component of lateral hypothalamic self-stimulation.

The effects of dopamine agonists on self-stimulation are a matter of considerable dispute. Apomorphine has variously been reported to inhibit, have no effect on, or to facilitate lever-press self-stimulation. To investigate the possibility that these discrepancies may reflect peculiarities of the lever-press test situation, the present study investigated the effects of apomorphine on locomotor initiation of and escape from lateral hypothalamic stimulation in a shuttle-box. Apomorphine had relatively little effect on the initiation behavior, but it produced a large and dose-dependent inhibition of escape. These data suggest that apomorphine acts to inhibit the aversive component of lateral hypothalamic stimulation. The implications of these findings for the usefulness of the shuttle-box in investigating the pharmacology of self-stimulation are discussed.

Animals↗
PubMed1980

The effect of thioridazine on prolactin levels in acutely schizophrenic patients: challenge-dose and steady-state levels.

Prolactin (PRL) levels in unmedicated male patients with acute schizophrenia were within normal range at baseline, increased five fold after a challenge dose of thioridazine, did not significantly increase further after therapeutic dosages, and remained elevated for the duration of treatment. The rise in PRL levels was significantly correlated with the steady-state plasma levels of thioridazine and/or mesoridazine. Baseline and challenge-dose PRL levels did not correlate with severity of symptoms as measured by the Brief Psychiatric Rating Scale, or predict response to thioridazine. Overall, there was a trend for the drug and PRL levels to increase very quickly and remain elevated while the clinical response was gradual over the four-week period. clinically, it may be useful monitoring PRL levels, since the therapeutic dosage should usually be above the dosage required to produce maximal PRL levels.

Acute Disease↗
PubMed1979

Onset of mania in bipolar manic-depressive patients.

Onset of mania was evaluated retrospectively in 48 bipolar manic-depressive patients. Mania occurred as the initial episode in 40% of cases. In patients with initial episode of depression, approximately 80% developed mania prior to their third episodes of depression and within 5 years from the onset of this illness. Differences in type of illness onset were related to family history of bipolar illness and sex of the proband. Male patients with a positive family history were significantly more likely to manifest mania at onset of illness.

Adult↗
PubMed1978

alpha-Adrenergic modulation of hypothalamic self-stimulation: effects of phenoxybenzamine, yohimbine, dexamphetamine and their interactions with clonidine.

The alpha-adrenoceptor agonist clonidine (12.5--50.0 microgram/kg) produced a dose-dependent increase in the latency to initiate lateral hypothalamic stimulation. The insurmountable postsynaptic alpha-adrenoceptor antagonist phenoxybenzamine (0.2-0.8 mg/kg) had no effect on self-stimulation by itself, but potentiated the inhibitory effects of clonidine. The fact that the concurrent escape behavior to the intracranial stimulation was unchanged by either clonidine or the phenoxybenzamine-clonidine combination suggests that the inhibition is specific to the rewarding component of hypothalamic stimulation. Yohimbine (0.5--2.0 mg/kg) produced a dose-dependent increase in both response latencies. This lack of behavioral specificity may reflect yohimbine's wide range of pharmacological activity, Dexamphetamine (0.25--0.50 mg/kg) reversed clonidine's inhibition of self-stimulation reward in a specific and dose-dependent fashion. This reversal could be blocked by previous inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. These data support the concept that the alpha-adrenoceptors play a critical role in the modulation of hypothalamic self-stimulation reward. They further suggest that the inhibitory effects of clonidine on self-stimulation reward represent an agonist effect on presynaptic alpha-adrenoceptors.

Animals↗
PubMed1976

Alpha-noradrenergic modulation of hypothalamic self-stimulation: studies employing clonidine, 1-phenylephrine and alpha-methyl-p-tyrosine.

An alpha-noradrenergic substrate of rewarding intracranial stimulation (ICS) has been hypothesized based on the observation that the alpha-antagonist phentolamine produced an inhibition of self-stimulation. The present experiment investigated the effects on hypothalamic self-stimulation of the alpha agonist clonidine in normal and in catecholamine-depleted rats. Using a shuttle-box technique that provides a rate-independent index of the rewarding and aversive components of ICS, it was demonstrated that clonidine produces a dose-dependent inhibition of reward that is clearly dissociable from any non-specific effects of the drug. The ineffectiveness of the peripheral alpha-agonist 1-phenylephrine indicates that the inhibition of reward produced by clonidine is mediated centrally. Clonidine and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine act together in a synergistic manner to greatly increase the magnitude and prolong the duration of the inhibition of reward while leaving the aversive component unaffected. These data are interpreted as supporting an alpha-noradrenergic basis of ICS reward while indicating that the aversive component of ICS is essentially independent of noradrenergic transmission.

Animals↗