PubMed Health⌕ Search

Biomedical subjects

A Clow

Publications and source records attributed to A Clow.

At least 73 records · Page 4Linked to original sources
PubMed1983

Current genetic and biological approaches to alcoholism.

Three out of 4 adoption and 2 out of 3 twin studies imply a genetic contribution to alcoholism in males. A recent study of moderate drinking in male twins suggests that familial factors account for some two-thirds of the variance in alcohol consumption, and that the genetic component slightly outweighs the effects of the within family culture. There has been little support for the notion of a genetic entity which expresses itself as alcoholism in males and depressive illness in females, but among normal male twins anxiety and depression are genetically correlated with alcohol consumption. Increased liability to form acetaldehyde and the potentially additive tetrahydroisoquinolines could be one factor predisposing to alcoholism but human studies have been less convincing than their animal counterparts.

Alcohol Drinking↗
PubMed1982

Raised endogenous monoamine oxidase inhibitor output in postwithdrawal alcoholics: effects of L-dopa and ethanol.

Urinary output of endogenous monoamine oxidase inhibitor was significantly greater in a group of postwithdrawal alcoholics than in controls. An oral dose of 0.5 g of L-dopa reduced output to control values in the alcoholics, but in the controls themselves output was unaffected. A similar excretion pattern to unextracted samples was observed in ethyl acetate extracts of these urine samples, acidified to pH 1. In a second group of postwithdrawal alcoholics, where the L-dopa effect was confirmed, ethanol administration brought about a small but not significant reduction in inhibitor output.

Adult↗
PubMed1981

Neuroleptic-induced acute dystonic reactions may be due to enhanced dopamine release on to supersensitive postsynaptic receptors.

Oral administration of butaperazine (40 mg per kilogram) to rats increased dopamine turnover, as measured by elevation of striatal and mesolimbic concentrations of homovanillic acid and 3,4-dihydroxyphenylacetic acid, for 24 to 48 hours. Initially, this dose of butaperazine inhibited stereotyped behavior in response to subcutaneous administration of apomorphine, but this effect was reversed at 12 hours. Later, animals had normal or exaggerated responses to apomorphine. The data suggest that the critical 20- to 28-hour period after butaperazine administration, when most human acute dystonic reactions occur, normal or supersensitive cerebral dopamine receptors are exposed to an excessive synaptic release of dopamine. This may be responsible for the drug-induced dystonia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Changes in rat striatal dopamine turnover and receptor activity during one years neuroleptic administration.

Administration of trifluoperazine (2.5--3.5 mg/kg/day p.o.) or thioridazine (30--40 mg/kg/day) for up to 1 year initially increased homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations in striatum. However, by 1 month and thereafter metabolite levels returned almost to control values. Dopamine concentrations were elevated after 3 months administration of both drugs and also after 12 months administration of trifluoperazine. Trifluoperazine administration for 1 month produced a marked increase in the dissociation constant (KD) for striatal 3H-spiperone binding but a reduction in receptor numbers. Thereafter receptor numbers increased at 6 and 12 months in both trifluoperazine and thioridazine treated animals compared to control values. The KD for both drug treated groups returned to normal at 6 months; however, by 12 months drug treated animals again demonstrated high KD values. Dopamine stimulation of striatal adenylate cyclase was inhibited after administration of trifluoperazine or thioridazine for 1 week or 1 month. However, by 6 and 12 months this effect was replaced by an enhanced stimulation. Administration of lower doses of trifluoperazine (0.7--0.9 mg/kg/day p.o.) or thioridazine (6--9 mg/kg/day p.o.) for up to 1 year produced similar although generally less marked changes in these biochemical indices of dopamine function. This study provides evidence of biochemical changes which parallel the behavioural findings of enhanced dopamine receptor activity that occur during continuous long-term neuroleptic administration to rodents.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Cerebral dopamine function in rats following withdrawal from one year of continuous neuroleptic administration.

Continuous administration of trifluoperazine (2.5--3.5 mg/kg/day) or thioridazine (30--40 mg/kg/day) to rats for 12 months enhanced the stereotyped response to apomorphine (0.5 mg/kg s.c.), increased dopamine 1--150 muM) stimulation of striatal adenylate cyclase, increased KD and Bmax for dopamine (10(-4) M) specific 3H-spiperone striatal binding and produced spontaneous mouthing movements. On drug withdrawal, spontaneous locomotor activity was enhanced after 2 weeks and the enhanced stereotyped response was maintained for up to 1 month. Spontaneous mouthing had disappeared 2 weeks after drug withdrawal. The increase in Bmax for 3H-spiperone binding was maintained for up to 3 months after drug removal, but KD reverted to control levels by 2 weeks. In contrast, the dopamine stimulation of striatal adenylate cyclase remained enhanced for the 6 month withdrawal period. Administration of trifluoperazine (0.7--0.9 mg/kg/day) or thioridazine (6--8 mg/kg/day) for 12 months produced a less marked effect than administration of the higher dose. No enhancement of effect was observed on drug withdrawal and the initial changes disappeared rapidly on removal of drug. Supersensitivity of striatal dopamine mechanisms produced by continuous long-term neuroleptic administration differs from that produced by shorter treatment periods since no enhancement of effect occurs on drug withdrawal. The behavioural and biochemical components of the supersensitivity show variable time courses and in particular the enhanced stimulation of striatal adenylate cyclase persists for at least 6 months. Such effects may be of relevance to tardive dyskinesias in man.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

A comparison of striatal and mesolimbic dopamine function in the rat during 6-month trifluoperazine administration.

Previous work has shown that 6---12 months continuous trifluoperazine (TFP) administration to rats causes striatal dopamine receptor supersensitivity. We have now replicated our original findings in the striatum and report concurrent changes in mesolimbic dopamine function during chronic TFP (2.8---4.0 mg/kg/day) administration for 6 months. Initial inhibition of apomorphine-induced stereotyped behaviour, which lasted for 2 weeks after the beginning of drug administration, was replaced by an exaggerated response to apomorphine (0.5 mg/kg SC) after 6 months drug intake. Striatal dopamine sensitive adenylate cyclase activity was inhibited at 1 and 3 months, but y 6 months was enhanced compared to control values. Mesolimbic adenylate cyclase activity was inhibited after 2 weeks and thereafter returned to control levels. Dopamine-identified 3H-spiperone binding sites (Bmax) in the striatum were increased by 2 weeks, reduced at 1 month and increased again at 6 months. In mesolimbic areas Bmax was increased at 2 weeks and 1 month but thereafter returned to control levels. The dissociation constant (kD) of specific 3H-spiperone binding was increased in the striatum and mesolimbic areas at 1 month and 2 weeks respectively. The results show differential changes in dopamine function in striatal and mesolimbic brain areas during 6 months continuous TFP administration to rats.

Adenylyl Cyclases↗
PubMed1979

Changes in dopamine-mediated behaviour during one year's neuroleptic administration.

Trifluoperazine (2.5--3.5 mg/kg/day) or thioridazine (30--40 mg/kg/day) were given in the drinking water to male Wistar rats for 12 months. Initial catalepsy and inhibition of spontaneous locomotion disappeared by 3 months and thereafter. Initial inhibition of stereotypy induced by s.c. apomorphine also disappeared by 3 months to be replaced by an enhanc-d stereotypy response after 6 and 12 months' drug intake. Drug-treated animals exhibited a greatly increased incidence of spontaneous mouth movements after 12 months' intake compared with control animals. Lower doses of both drugs (trifluoperazine 0.7--0.9 mg/kg/day; thioridazine 6--8 mg/kg/day) also initially suppressed behavioural responses but by 1 month and thereafter these animals were indistinguishable from controls. At 12 months, however, these animals also exhibited an increased incidence of spontaneous mouth movements. The data demonstrate a reversal of the initial dopamine receptor-blocking properties of trifluoperazine or thioridazine to be replaced by an enhanced response of cerebral dopamine systems while animals were still continuously receiving the drug.

Animals↗