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C J Fowler

Publications and source records attributed to C J Fowler.

At least 217 records · Page 12Linked to original sources
PubMed1987

Comparison of the effects of dopamine D1 and D2 receptor antagonists on rat striatal, limbic and nigral dopamine synthesis and utilisation.

The effects of dopamine (DA) antagonists upon DA synthesis and utilisation in the rat striatum, olfactory tubercle and substantia nigra have been studied. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the rate of depletion of DA after in vivo inhibition of tyrosine hydroxylase by H44/68, and the accumulation of L-DOPA after in vivo inhibition of l-aromatic amino acid decarboxylase by NSD 1015 were measured in the study. Haloperidol (0.23 mumol/kg i.p.), sulpiride (293 mumol/kg i.p.) and remoxipride (5.6 mumol/kg i.p.) increased both DA synthesis and utilisation in the striatum and olfactory tubercle. A lower dose of sulpiride (45 mumol/kg i.p.) increased DA synthesis and utilisation in the olfactory tubercle alone. None of the compounds, at the doses used, affected either DOPAC and HVA concentrations or the rate of utilisation of DA in the substantia nigra. Sulpiride (293 mumol/kg i.p.) and remoxipride, however, produced a modest rise in nigral DA synthesis. The dopamine D 1-selective antagonist SCH 23390 had only modest effects on striatal, limbic and nigral DA synthesis and utilisation at the doses tested (0.078 and 0.36 mumol/kg i.p.).

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Dopamine turnover and glutamate decarboxylase activity in the rat brain after acute and chronic treatment with raclopride, a dopamine D2-selective antagonist.

The effect of acute and chronic (94, 141 and/or 199 days) oral treatment of rats with the dopamine D2-selective antagonist raclopride (0, 5, 15, 45 and 135 mumol/kg) upon the turnover of dopamine in the striatum and limbic system and upon the activity of glutamate decarboxylase (GAD) in the s. nigra, striatum and frontal cortex has been investigated. A dose-dependent tolerance to the effect of raclopride on the turnover of dopamine was observed after chronic treatment, although the degree of tolerance was marginal at the 5 and 15 mumol/kg doses. Acute treatment with raclopride was without effect on the activity of GAD in the s. nigra, striatum or frontal cortex, whereas chronic (199 days) treatment with 45 mumol/kg of raclopride produced an increase in the activity of GAD in the s. nigra and striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Repeated testing of rats markedly enhances the duration of effects induced by haloperidol on treadmill locomotion, catalepsy, and a conditioned avoidance response.

In the present experiments we have investigated the duration of haloperidol-induced effects in rats tested repeatedly, and in rats tested on a single occasion after drug administration. The behavioral test situations used include treadmill locomotion (speed 4 m/min), inclined grid catalepsy, two-way conditioned avoidance behavior and open field spontaneous locomotor activity. It was found that the duration of haloperidol-induced effects on treadmill locomotion, spontaneous locomotor activity, catalepsy and a conditioned avoidance response (doses: 0.32, 0.32, 1.25 and 0.2 mg/kg IP, respectively) was about 2 hr or less in animals observed once only ("independent procedure"). With the possible exception for locomotor activity, the duration of haloperidol-induced effects was considerably prolonged, up to 8 hr depending on the test situation, in animals observed repeatedly after the administration of haloperidol in the same doses ("dependent procedure"). The enhanced duration by the dependent procedure is probably not caused by handling stress since the enhanced duration of haloperidol-induced effects in some of the behavioral tests were only noted in animals tested repeatedly in one particular test, and not in animals given the repeated pretests in another situation. Furthermore, it was not possible to relate the enhanced duration of haloperidol-induced effects by repeated testing to changes in striatal DA metabolism as evaluated by measurements of DOPAC, HVA and DA. It was found that the treadmill test 2-4 hr after haloperidol (0.12-0.32 mg/kg IP), at certain doses and time intervals produced an increase in DA turnover [(DOPAC + HVA)/DA], but this increase was the same in both procedures (dependent and independent).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Antagonist effects of the enantiomers of 3-PPP towards alpha 1-adrenoceptors coupled to inositol phospholipid breakdown in the rat cerebral cortex.

The effects of the two enantiomers of 3-PPP upon alpha 1-adrenergic and muscarinic receptors coupled to the inositol phospholipid (PI) breakdown response have been investigated. 3-PPP(-) and 3-PPP(+) were found to antagonize the noradrenaline (10 microM)-stimulated PI breakdown in rat cerebral cortical miniprisms with IC50 values of 18 and 61 microM, respectively. The dopamine receptor antagonists haloperidol and raclopride were also antagonists, with IC50 values of 0.4 and 25 microM, respectively. 3-PPP(-) and raclopride were found further to act as competitive antagonists, with pA2 values of 6.03 and 5.44, respectively. 3-PPP(-), 3-PPP(+) and haloperidol also antagonized the muscarinic receptor-mediated carbachol (50 microM)-stimulated PI breakdown in cortical miniprisms, albeit at high concentrations (IC50 values of 91, 170 and 28 microM, respectively) whereas raclopride produced only 24% inhibition at the highest concentration tested (100 microM).

Animals↗
PubMed1987

Stimulation of inositol phospholipid breakdown in rat cortical and hippocampal miniprisms by noradrenaline, 5-hydroxytryptamine and carbachol: some methodological aspects.

After incubation of miniprisms from rat cerebral cortex or hippocampus with 3H-myo-inositol, labelling of the phospholipid ("Lipid") and inositol phosphate ("InsP") fractions was found. Inositol phospholipid hydrolysis ("PI breakdown") was stimulated by noradrenaline, 5-hydroxytryptamine and carbachol. Expressing data as InsP/(Lipid + InsP) was found to be a superior measure of the rate of PI breakdown compared with the more commonly used InsP d.p.m. unit, since the former was found to be independent of the volume of the miniprism aliquot used and the degree of labelling of inositol phospholipids. The PI breakdown responses to noradrenaline, 5-hydroxytryptamine and particularly carbachol were found to be enhanced by increasing the assay [K+] from 5.88 mM to 18.2 mM. Storage of hippocampal samples at -70 degrees by the "slow freeze-fast thaw" method of Hardy et al. (1983) resulted in a decreased degree of labelling of the Lipid and InsP fractions and a loss of the PI response to noradrenaline when assayed at a [K+] of 5.88 mM, but a reasonable response was seen in these samples at an assay [K+] of 18.2 mM. The temperature of the Krebs-Henseleit buffer used in the preparation of the miniprisms was found to be important for the PI breakdown response.

Animals↗
PubMed1987

Investigation into the effects in-vitro of the 5-hydroxytryptamine reuptake inhibitor, alaproclate, on carbachol-stimulated inositol phospholipid breakdown in the rat cerebral cortex.

The effect of alaproclate in carbachol-stimulated inositol phospholipid (PI) breakdown in rat cerebral cortical miniprisms has been investigated. Carbachol-stimulated PI breakdown was greatly enhanced by increasing the assay potassium concentration from 5.88 to 18.2 mM. Alaproclate, on the other hand, did not influence carbachol-stimulated PI breakdown over the concentration range tested (0-100 microM) at either assay [K+]. The elution pattern of the inositol phosphates from the Dowex-1 columns was also unaffected by alaproclate both in the absence and presence of carbachol. Thus, the potentiation by alaproclate of tremor and salivation induced by the muscarinic agonist oxotremorine in-vivo reported previously is not seen when muscarinic function is measured in-vitro using carbachol-stimulated PI breakdown.

Alanine↗
PubMed1987

A portable system for measuring cutaneous thresholds for warming and cooling.

Measurement of cutaneous thermal thresholds is a valuable technique for detecting small fibre neuropathy. A robust and portable microcomputer controlled system, which separately measures thresholds for warming and cooling, is described. Thresholds at three sites have been measured; the cheek, the dorsum of the hand and the sole of the foot. Regional variability and a correlation with age have been found, indicating the sensitivity of this system.

Computers↗
PubMed1986

Electromyography of urethral sphincter in women with urinary retention.

Concentric-needle electromyography (EMG) of the urethral sphincter muscle was carried out in 48 women with urinary retention. Changes in motor unit configuration indicating reinnervation were found in 16 women, and myotonic-like EMG activity, which may impair urethral relaxation, in 19 women. Sphincter EMG was normal in 13 cases. The finding of a significant abnormality in 72% of cases calls into question the validity of the commonly applied diagnosis of psychogenic urinary retention.

Electromyography↗
PubMed1986

Seasonal variations in the stability of monoamines and their metabolites in perchloric acid as measured by high-performance liquid chromatography.

The stability in acid medium of dopamine, dihydroxyphenylacetic acid (DO-PAC), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was investigated. The stability of 5-HT and 5-HIAA was poor, but could greatly be improved by the addition of sodium bisulphite and disodium edetate. Under these conditions, dopamine, DOPAC, HVA, 5-HT and 5-HIAA showed good stability over 24 h at room temperature throughout the year when stored in capped vials. In uncapped vials, the stability of 5-HT and 5-HIAA was reasonable during the winter months, but was poor during the summer months.

Biogenic Amines↗
PubMed1986

The effect of selective noradrenergic lesions upon the stimulation by noradrenaline of inositol phospholipid breakdown in rat hippocampal miniprisms.

The breakdown of inositol phospholipid (PI) stimulated by hippocampal noradrenaline in rat miniprisms in vitro was used as an index of alpha 1-adrenoceptor function after selective noradrenergic denervation. Selective denervation was produced by microinjections of 6-hydroxydopamine (6-OHDA) into either the dorsal noradrenergic bundle (DNAB) or the locus coeruleus (LC), or by systemic treatment with the noradrenergic neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine). Fourteen days after these treatments, there was a large depletion of cortical noradrenaline but no change in the stimulation of hippocampal PI breakdown by noradrenaline. It is concluded that selective noradrenergic denervation under the conditions used here does not lead to hippocampal alpha 1-adrenoceptor supersensitivity as assessed by noradrenaline-stimulated PI breakdown.

Animals↗
PubMed1986

Raising the ambient potassium ion concentration enhances carbachol stimulated phosphoinositide hydrolysis in rat brain hippocampal and cerebral cortical miniprisms.

The influence of the ambient potassium ion concentration ([K+]) upon agonist stimulated hydrolysis of phosphoinositides (PI) has been studied in isolated miniprisms of rat hippocampus and cerebral cortex. When the external [K+] was raised from 6 to 18 mmol/l, there was little or no increase in the hydrolysis of PI in the absence of agonist, however, carbachol (100 mumol/l) stimulated hydrolysis was greatly enhanced in both brain regions studied. Thus, carbachol stimulated the hydrolysis of PI to 146% and 386% of control levels at potassium concentrations of 5.88 and 18.2 mmol/l, respectively, in the rat hippocampus. A similar enhancement of muscarine (100 mumol/l) stimulation was observed in cortical miniprisms with 18 mmol/l [K+]. A further enhancement was seen at higher ambient [K+], although basal hydrolysis of PI was then also increased. The carbachol-stimulated hydrolysis of PI found at both 6 and raised [K+] was prevented by atropine (1 and 10 mumol/l) and tetraethylammonium (20 mmol/l), but not by 10 mmol/l Mg2+. Pirenzepine (50 nmol/l) also reduced this response. The ions Cs+ and Rb+ (but not Li+ or Tris+) produced a similar enhancement of the carbachol stimulation to that found with K+. At a buffer [K+] of 6 mmol/l, noradrenaline (100 mumol/l) produced a 2-fold increase in the hydrolysis of PI whereas 5-hydroxytryptamine (100 mumol/l) and histamine (500 mumol/l) had little or no effect. However, histamine and 5-hydroxytryptamine did stimulate the hydrolysis of PI when [K+] was increased. Miniprism ATP content was not changed by a rise in [K+] to 18 mmol/l. The significance of these results is discussed in terms of the postsynaptic cellular events following cholinergic stimulation.

5-Hydroxytryptophan↗
PubMed1986

The effect of the dopamine agonist pergolide on tyrosine hydroxylase activity in rat striatal and limbic miniprisms in vitro: a model for the dopamine autoreceptor?

A method for the assay of tyrosine hydroxylase activity in rat striatal and limbic (nucleus accumbens + olfactory tubercle) brain miniprisms is described. The dopamine agonists apomorphine (1 mumol/l) and pergolide (0.01-100 mumol/l) inhibited the tyrosine hydroxylase activity in both regions. The inhibition produced by 1 mumol/l pergolide was antagonised partially in striatal miniprisms and completely in limbic miniprisms by 1 mumol/l haloperidol. The dopamine D2-selective antagonist raclopride, at concentrations up to 300 nmol/l, did not antagonise the inhibition produced by pergolide in striatal miniprisms, but appeared partially to antagonise the inhibition in limbic miniprisms. It is concluded that whilst pergolide potently inhibits tyrosine hydroxylase activity in striatal and limbic miniprisms, the inhibition is of doubtful value as a predictive model of dopamine autoreceptor function in striatal miniprisms, but may be useful when limbic miniprisms are used.

Animals↗
PubMed1986

Noradrenaline-stimulated inositol phospholipid breakdown as a measure of alpha 1-adrenoceptor function in rat hippocampal miniprisms after repeated antidepressant treatment.

Noradrenaline-stimulated inositol phospholipid (PI) breakdown in rat hippocampal miniprisms was used as a measure of alpha 1-adrenoceptor function after repeated antidepressant treatment. After 24-29 days of oral treatment with either desipramine, mianserin, maprotiline or zimeldine (all at doses of 10 mg/kg b.i.d.), there was no significant difference in the degree of stimulation of hippocampal PI breakdown by 0.4, 2, 10 or 100 microM noradrenaline. It is concluded that there is no supersensitivity of hippocampal alpha 1-adrenoceptors coupled to PI breakdown after repeated antidepressant treatment under the conditions used.

Animals↗
PubMed1986

EEG changes in subcortical dementia: a study of 22 patients with Steele-Richardson-Olszewski (SRO) syndrome.

To assess the value of EEG in distinguishing between cortical and subcortical dementia, we compared the EEGs of 22 patients with SRO syndrome with those of 22 patients who had a comparable degree of dementia due to cortical atrophy. EEG records from patients with SRO syndrome were of low voltage, but with preserved alpha rhythm at 8-10 Hz and were within normal limits in 12/22. In 8 there was an abnormal excess of theta activity and one had additional lateralizing asymmetries. One had frontal intermittent rhythmic slow wave activity. Comparison with records of 22 patients, with cortical atrophy due to Alzheimer's disease but with only mild to moderate dementia, showed a similar low frequency of non-specific abnormalities.

Cerebral Cortex↗
PubMed1986

Dopamine D2 receptors and dopamine metabolism. Relationship between biochemical and behavioural effects of substituted benzamide drugs.

The effect of the substituted benzamide dopamine D2 receptor antagonists sulpiride, raclopride, FLA 966(-), FLA 988(-), eticlopride and remoxipride as well as the "classical" dopamine antagonists, haloperidol and chlorpromazine, on the concentrations of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of the rat was investigated. All compounds increased the turnover of dopamine, as defined by increased concentrations of DOPAC and HVA (without change in the concentration of dopamine) in the striatum in a dose-dependent manner. The doses of the compounds producing increased turnover of dopamine in the striatum were in the same range as those displacing the in vivo binding of [3H]spiperone in the striatum. In addition, for all the compounds tested in the study, an increase in the turnover of dopamine to about 300% of control was observed for doses antagonising the stereotypy produced by the dopamine agonist, apomorphine. On the other hand, no consistent relationship between increased turnover of dopamine and the doses of the compounds required to antagonise apomorphine-induced hyperactivity was found. This result was also found in limbic areas. Remoxipride and haloperidol had little or no effect on the turnover of dopamine in either the hypothalamus or substantia nigra at the ED50 doses of these compounds for antagonism of apomorphine-induced stereotypy.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Cortical beta- and alpha 2- adrenoceptor binding, hypothalamic noradrenaline and pineal melatonin concentrations measured at different times of the day after repeated treatment of rats with imipramine, zimeldine, alaproclate and amiflamine.

The effect of repeated treatment of rats for 21 days with the monoamine reuptake inhibitors imipramine, zimeldine, alaproclate (in each case 10 mumol/kg b.i.d.) and the reversible monoamine oxidase-A inhibitor amiflamine (3 mumol/kg b.i.d.) on brain noradrenergic mechanisms measured at different times of the day and night was investigated. Imipramine treatment produced a down-regulation of the Bmax for 3H-dihydroalprenolol binding to cortical beta-adrenoceptors that was not dependent upon the time of day the animals were killed. Zimeldine, on the other hand, reduced both Bmax and Kd of binding for day-time, but not night-time samples. Alaproclate and amiflamine were without effect on the binding. Twenty-four hour mean values for 1 nM 3H-p-aminoclonidine binding to alpha 2-adrenoceptors were lower for the zimeldine-treated rats than for the saline-treated rats. Pineal melatonin concentrations, which are regulated by beta-adrenoceptors, showed a pronounced diurnal rhythm, with the highest concentrations being found at 02:00. At this time point, a lower pineal melatonin content was found after amiflamine treatment, whereas imipramine, zimeldine and alaproclate were without significant effect. The importance of the use of more than one time point and the use of more than one biochemical test for the determination of the effects of repeated antidepressant treatment on central noradrenergic systems measured ex vivo is discussed.

Alanine↗