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Biomedical subjects

H F Baker

Publications and source records attributed to H F Baker.

At least 109 records · Page 6Linked to original sources
PubMed1982

Studies on the accessibility of prolactin and growth hormone to brain: effect of opiate agonists on hormone levels in serial, simultaneous plasma and cerebrospinal fluid samples in the rhesus monkey.

The accessibility of prolactin and growth hormone to the cerebrospinal fluid (CSF) was investigated in rhesus monkeys fitted with reservoirs connected to catheters placed in the fourth ventricle. Simultaneous blood and CSF samples were collected after opiate agonists. There was a brisk, marked rise in plasma prolactin following i.v. morphine sulphate which was followed by a slower, lesser rise in CSF prolactin. After i.v. D-Ala2,MePhe4,Met-O-(ol)-enkephalin (DAMME, FK 33-824, Sandoz) two animals responded similarly but the third showed a much smaller plasma and absent CSF response. Growth hormone showed inconsistent plasma patterns after morphine but a late rise following DAMME; however, CSF growth hormone did not change. Infusion of exogenous human prolactin produced plasma and CSF prolactin levels of similar magnitude and time-course as following opiate agonists. Infusions of larger amounts of purified human growth hormone greatly elevated plasma levels but only led to modest increases in CSF growth hormone. It is concluded that prolactin has relatively ready access to CSF, especially in comparison to growth hormone. The possible significance and mechanisms are discussed.

Animals↗
PubMed1982

Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey.

Five vervet monkeys were administered increasing doses (4--12 mg/kg/day) of d-amphetamine over a period of 35 days. Three phases od behavioural change were discerned: phase 1 during which animals exhibited repetitive stereotyped action sequences with rapid head movements, occasional abnormal grooming, picking at the cage, hand-staring and snatching; phase 2 in which behaviour became progressively more restricted and animals became markedly unresponsive to auditory, visual and tactile stimuli; phase 3 was characterised by the abrupt development of gross over-responsiveness to environmental stimuli, ataxia and tremor. At post-mortem, by comparison with controls, amphetamine-treated monkeys showed marked depletions of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in corpus striatum and cerebral cortex and reductions in the activities of tyrosine hydroxylase and dopa decarboxylase in striatum. Turnover of these monoamines, assessed by high-performance liquid chromatography determinations of their respective metabolites, was also reduced. These findings are interpreted as evidence of monoamine neurone destruction, most severely in the case of DA neurones. Though there was a non-significant reduction in 3H-spiperone binding (reaching almost 50% in nucleus accumbens), numbers of receptors for the monoamines nA and 5-HT were not significantly changed, and the activities of the enzymes choline acetyltransferase and glutamine decarboxylase were similar in experimental and control animals. The contrast of these findings with those seen in post-mortem brains in schizophrenia is discussed.

Animals↗
PubMed1982

Stereotypy in monkeys and humans.

Stereotyped movements are described in monkeys and humans and are classified as arising from constraint, sensory deprivation in infancy, amphetamine treatment or psychotic states. It is argued that, with the exception of cage stereotypies, stereotyped behaviour is evidence of abnormality in the nervous system consequent upon distorted maturational processes, organic defect or biochemical disturbance. Stereotypy is associated with a state of cognitive inflexibility and social and sensory isolation in humans and monkeys. It is suggested that, while no simple biochemical disturbance in the brain can describe these various occurrences of stereotypy, the cross-species occurrence of a syndrome of isolation, cognitive inflexibility and stereotypy implies a related mechanism mediating these divergent effects. If stereotypy is regarded as a consequence of failure to use sensory input to direct behaviour, therapeutic regimes designed to stimulate responsive behaviours and social interactions are more likely to be effective in the long run than direct attempts to suppress stereotypy.

Amphetamine↗
PubMed1981

Effect of chronic amphetamine administration on central dopaminergic mechanisms in the vervet.

A biochemical study of central dopaminergic mechanisms was carried out in brain tissue from vervet monkeys who had been subjected to chronic amphetamine administration. The brain concentrations of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were markedly reduced. Significant reductions were also observed in the activities of dopa-decarboxylase (DDC) and tyrosine hydroxylase (TH). A kinetic study of TH revealed a 60% reduction in maximum reaction velocity, consistent with destruction of DA neurones. However, homovanillic acid (HVA) concentrations were only moderately reduced, suggesting a nearly normal production of DA. Hence despite the large depletions in DA concentrations, high affinity binding of 3H-spiperone binding to striatal DA receptors was no different from controls. The results are discussed in relation to the amphetamine psychosis in humans.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

An involvement of dopamine in higher order choice mechanisms in the monkey.

Low doses of amphetamine induce choice perseveration in an object discrimination task under conditions where such perseveration either increases or decreases the number of rewards obtained as compared to chance performance. Neither stereotyped motor actions nor repetitive choice of position contributed to this effect which could be blocked by pre-treatment with the neuroleptic haloperidol. These results demonstrate that higher order choice mechanisms may involve dopamine systems in the primate.

Animals↗
PubMed1981

Perseverative behaviour after amphetamine; dissociation of response tendency from reward association.

Low doses of amphetamine were found to alter the ability of marmosets to take account of changes in reward values of object stimuli in a visual discrimination task. Under amphetamine, animals changed their motor responses and stimulus choice in order to preserve the acquired reward value or meaning of certain stimuli. These results suggest that the perseverative effect of amphetamine on behaviour is due to impaired cognitive flexibility rather than to an enhancement of motor habit.

Animals↗
PubMed1981

A new approach to the role of noradrenaline in learning: problem-solving in the marmoset after alpha-noradrenergic receptor blockade.

Nine marmosets (Callithrix jacchus) were tested on a variety of visual discrimination learning tasks in a Wisconsin General Test Apparatus with or without alpha-noradrenergic receptor blockade achieved by the administration of aceperone. After aceperone, animals were found to be severely and consistently impaired at learning the first task of each test session and to be impaired on new and repeated reversal learning. They were, however, unimpaired on learning another similar task in each test session and on performance of a well-learnt task. Results were interpreted as evidence for defective association formation which can be compensated for by suitable priming or practice.

Adrenergic alpha-Antagonists↗
PubMed1981

An analysis of visual object reversal learning in the marmoset after amphetamine and haloperidol.

The effect of amphetamine and haloperidol pretreatment on visual object reversal learning was assessed in the marmoset. Amphetamine induced perseverative responding demonstrated by high reversal learning scores and worse than chance performance in the early stages of reversal. This perseverative responding was prevented by pretreatment with haloperidol. Haloperidol, either alone or in conjunction with amphetamine caused a mild, non-perseverative impairment on reversal learning only.

Amphetamine↗
PubMed1980

Amphetamine disrupts successive but not simultaneous visual discrimination in the monkey.

Three adolescent marmosets were trained on simultaneous and successive versions of a red-white visual discrimination task. The effects of doses of 0.2-1.2 mg/kg D-amphetamine on the performance of these tasks were assessed using a balanced design. It was found that while there was no drug effect on performance of the simultaneous task, amphetamine exerted a dose dependent disruptive effect on the successive version of the task. It is argued that amphetamine disrupts response control rather than discriminative ability and, in this respect, resembles the effect of orbitofrontal and limbic lesions in contrast to other neocortical lesions.

Animals↗
PubMed1980

"Go here-to there" performance after amphetamine: the importance of the response requirement in successive discrimination.

Marmosets were trained on a task involving simultaneous and successive visual discrimination performance where responses were required on all trials. Performance of this task was not affected by low doses of amphetamine. From this it is concluded that amphetamine does not cause a narrowing of attention and that the disruptive effect of amphetamine on the "go-no go" successive discrimination task already reported is due to a loss of response inhibition rather than to difficulties in the recognition of stimuli presented without a comparison stimulus.

Amphetamine↗
PubMed1980

The effect of amphetamine on delayed response performance in the monkey.

The effect of amphetamine on discrete-trial, visual discrimination where response was permitted simultaneously with stimulus presentations or 0, 1, or 3 sec after stimulus presentation, was assessed in the marmoset. An interaction between dose and delay was observed comprising significantly impaired performance after amphetamine under conditions of longer delay. Results are interpreted in terms of loss of response inhibition and increased distraction and are compared with frontal lobe function in the primate.

Amphetamine↗
PubMed1980

The effects of metoclopramide, sulpiride, and the stereoisomers of baclofen on amphetamine-induced behavior in the marmoset.

We have studied the effects on amphetamine-induced behavior in a primate species of drugs (other than the classic neuroleptics) sometimes used in the treatment of psychosis. Marmosets were treated with either saline (control animals) or amphetamine followed after 18 min by doses of either metoclopramide, sulpiride, or the d- or l-isomers of baclofen. Metoclopramide antagonized amphetamine-induced behavior at low doses while also causing sedation at higher doses in control animals. Neither sulpiride nor baclofen specifically antagonized amphetamine-induced behavior.

Amphetamine↗
PubMed1979

Modification of the behavioural effects of amphetamine by a GABA agonist in a primate species.

Acute administration of d-amphetamine in the marmoset results in a dose dependent increase in small head movements (checking), and an almost total suppression of purposeful activities and social interaction. It has little effect on locomotion and does not induce stereotyped gnawing. The GABA-agonist, muscimol, decreases checking, locomotion, activities and social interaction when given alone, but induces jerking movements at large doses. When administered in combination with amphetamine, muscimol induces persistent stereotyped gnawing. On the basis of the present findings and those of experiments in rodents it is suggested that compulsive gnawing results from overactivity in the striatal efferent pathway, while checking is probably mediated by extra-striatal sites. Since the behavioural effects of muscimol resemble those of the typical neuroleptics with the exception of the induction of gnawing, it is suggested that muscimol, though sedative, may counteract certain extrapyramidal effects of neuroleptic treatment while facilitating their other behavioural effects.

Animals↗
PubMed1979

3-Methoxy-4-hydroxyphenylglycol excretion in acutely schizophrenic patients during a controlled clinical trial of the isomers of flupenthixol.

Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo. Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables. In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial. However in females no relationship between MHPG excretion and outcome was established. During the trial there was a reduction in MHPG excretion in patients treated with beta-flupenthixol but no decrease in the group treated with alpha-flupenthixol or chlorpromazine. In patients on placebo there was a reduction in MHPG excretion in those who did well clinically, but not in those who did poorly. Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia, but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration.

Adult↗
PubMed1979

Brain tryptophan metabolism in schizophrenia: a post mortem study of metabolites of the serotonin and kynurenine pathways in schizophrenic and control subjects.

Serotonin (5HT), its chief metabolite 5-hydroxyindoleacetic acid (5 HIAA), its precursor tryptophan, and kynurenine, another metabolite of tryptophan, have been measured in post mortem human brain samples. Concentrations of these metabolites were not found to be significantly different in putamen, hippocampus or temporal cortex from 23 normal subjects compared with 15 subjects in whom a diagnosis of schizophrenia could be restrospectively confirmed. The results have been analysed with respect to cause of death, medication and post mortem changes. Post mortem increases in tryptophan and kynurenine were observed. Some interrelationships between the variables measured within and between the different areas studied are discussed. It is concluded that there is no evidence for a generalised deficit of 5HT in the brain in schizophrenia, nor for gross changes in turnover along the serotonin or kynurenine pathways of tryptophan metabolism in brain.

Aged↗
PubMed1979

Interaction of apomorphine and haloperidol: effects on locomotion and other behaviour in the marmoset.

The behavioural effects of increasing doses of apomorphine and haloperidol were observed in a group of six marmosets. Behaviour was classified quantitatively into categories: Locomotion, inactivity, checking (small head movements), social interaction and purposeful activities. Statistical analysis revealed that apomorphine had a stimulant effect on checking and locomotion which could be antagonized by haloperidol. Activities and social contact were severly reduced by both apomorphine and haloperidol. Inactivity was increased by the lowest dose of apomorphine in otherwise untreated animals. It is suggested that haloperidol antagonizes the stimulant effects of apomorphine but is synergistic to its suppressant effects, and that the low dose effect of apomorphine on inactivity is mediated by a mechanism which may be different from that acted upon by haloperidol.

Animals↗