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Biomedical subjects

J M Murphy

Publications and source records attributed to J M Murphy.

At least 199 records · Page 11Linked to original sources
PubMed1987

Alcohol preference and regional brain monoamine contents of N/Nih heterogeneous stock rats.

The N/Nih heterogeneous stock rats were tested for alcohol drinking behavior. Rats that met criteria for high (greater than 5.0 g ethanol/kg body weight/day) and low (less than 0.5 g/kg/day) alcohol consumption were chosen, and the regional brain contents of monoamine neurotransmitters were determined in these animals. The primary finding was a lower content of serotonin and 5-hydroxyindoleacetic acid in the thalamus and hypothalamus of the high alcohol preferring N/Nih rats as compared with the low preferrers. The high preferrers were also found to have a lower content of dopamine and norepinephrine in the thalamus. The findings support the hypothesis that an inverse relationship exists between the density and/or metabolic functioning of regional brain serotonin systems and alcohol preference.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Rodent lines selected for factors affecting alcohol consumption.

The selectively bred alcohol-preferring P and alcohol-nonpreferring NP lines of rats have been used to study the biology of alcohol-seeking behavior. The P rats satisfy all the perceived criteria for an animal model of alcoholism: free-fed animals voluntarily drink alcoholic solutions (10-30% v/v) to intoxication; they acquire metabolic and neuronal tolerance, and develop physical dependence; they work (bar-press) to obtain the alcohol and self-administer ethanol intragastrically. Drinking in the P rats ceases when blood alcohol concentrations (BACs) reach 50-70 mg%, but BACs subsequently rise to as high as 270 mg%. BACs, 15-70 mg%, elicit increased spontaneous motor activity in the P rats, but not in the NP rats. Acute tolerance to a single hypnotic dose of ethanol develops more rapidly and persists many days longer in the P than in the NP rats. These differences in the effects of ethanol may underlie the disparate alcohol drinking behaviors of the P and NP rats. The P rats also exhibit lowered serotonin levels in certain brain regions. Serotonin reuptake inhibitors curtail the alcohol drinking of the P rats, suggesting a role for serotonin in alcohol preference.

Alcohol Drinking↗
PubMed1986

Effect of low dose ethanol on spontaneous motor activity in alcohol-preferring and -nonpreferring lines of rats.

To determine if behavioral arousal may be associated with ethanol preference, the effects of low to moderate doses of ethanol on spontaneous motor activity (SMA) were studied in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats as well as in the Maudsley Reactive (MR/N) and Nonreactive (MNR/N) strains. Alcohol-naive rats had food and water available ad lib, but food was removed 24 hr before and during activity testing. After an intraperitoneal injection of saline (5 ml) or ethanol (0.12 to 1.5 g/kg), SMA was monitored every three min for 30 min in an electronic activity monitor. The P and MR/N rats exhibited increased SMA after doses of 0.12 and 0.25 g/kg. Both the NP and MNR/N rats failed to show increased SMA at any ethanol dose. Moderate doses of ethanol, 1.0 and 1.5 g/kg, consistently depressed SMA in all lines/strains. In 24 hr-fasted rats, increased SMA occurred within 6-12 min after injection, but free-fed rats exhibited increased SMA 12-24 min after an ethanol dose of 0.25 g/kg. Free-choice drinking scores (10% ethanol (v/v) versus water) for the P, MR/N, MNR/N and NP rats were 6.6 +/- 0.5, 4.9 +/- 0.8, 2.2 +/- 0.7 and 1.4 +/- 0.3 g ethanol/kg body wt/day (mean +/- SEM), respectively. The data indicate a positive relationship between ethanol preference and ethanol-induced motor stimulation and suggest that hyperactivity may be an expression of the positive reinforcing effect of ethanol for alcohol-preferring rats.

Animals↗
PubMed1986

Brief psychosocial screening in outpatient pediatric practice.

The Pediatric Symptom Checklist (PSC) is a brief screening questionnaire designed to help pediatricians in busy office practice select children who are likely to have psychosocial difficulties and thus could benefit from further evaluation. We report two preliminary validation studies that indicate that PSC correlates well with the Childhood Behavior Checklist, a longer, well-validated questionnaire, and most children referred for psychiatric evaluation score above the PSC cutoff score. Developing a valid and practical psychosocial screening procedure for office practice is methodologically difficult but highly relevant to clinical practice.

Child↗
PubMed1986

Diagnosis and outcome: depression and anxiety in a general population.

An assessment of the long-term outcome for depression and anxiety disorders in a general population was made as part of the Stirling County Study. Measuring outcome as a dichotomy between experiencing recurrent episodes or not during a 17-year cohort interval, it was found that 56% of the 'cases' had a poor prognosis. While sex, age and level of severity were not significantly related to outcome, an initial diagnosis of depression was predictive of unfavourable prognosis. Only a few of these 'cases' received psychiatric specialty treatment. Some disorders in the community appear, however, to be as serious as those that come to the attention of psychiatrists.

Adaptation, Psychological↗
PubMed1986

Trends in depression and anxiety: men and women.

Recent reports from four longitudinal studies indicate that the epidemiology of depression and anxiety in general populations may have changed over the third quarter of this century. In each of two studies in the United States, one in Canada, and one in Sweden, more women than men at mid-century were found to have experienced depression and/or anxiety. By the end of the quarter, women and men in a few to several age groups were more equal in this regard than they had been earlier. In each study, interpretation was offered to the effect that social and historical changes may have contributed to these epidemiologic trends. The four studies are reviewed, and it is suggested that the findings deserve attention as generating hypotheses for further research.

Adult↗
PubMed1986

Studies on an animal model of alcoholism.

Past and ongoing studies indicate that the selectively bred P line of rats satisfies virtually all the suggested criteria for an animal model of alcoholism. They attain pharmacologically active levels of BAC and develop tolerance and physical dependence with voluntary oral ethanol ingestion, while in the free-feeding state. Ethanol is positively reinforcing to the P rats and consumption appears to be directed by the post-ingestive, pharmacological effects of ethanol, as revealed by the intragastric self-administration studies. Some interesting differences between the P and the NP lines have been uncovered. They differ in the content of serotonin in several brain regions and they respond differently to ethanol. The P rats develop acute tolerance to sedative-hypnotic doses of ethanol more rapidly than do the NP rats, and they exhibit stimulation with low doses of ethanol. These differences suggest hypotheses on mechanisms underlying alcohol-seeking behavior which can now be tested experimentally. It should be emphasized, however, that the described findings are the product of but a single genetic experiment. Clearly, replication is needed, and we are currently doing this, using a better defined, heterogeneous stock of rats. This one experiment, however, has demonstrated the feasibility of developing animal models of alcoholism and offers hope that the genetic and biological basis of alcohol-seeking behavior can be explored in the laboratory. The screening and testing of pharmacological agents able to deter alcohol-seeking behavior is an obvious practical application of this model.

Alcohol Drinking↗
PubMed1986

Diagnosis, screening, and 'demoralization': epidemiologic implications.

The Dohrenwends have associated psychiatric screening instruments with Frank's concept of 'demoralization' through negative evidence of the criterion validity of the instruments for identifying 'diagnosable mental disorders'. New evidence from the Stirling County Study is given to suggest that absence of validity stems from symptom-enumerative scoring procedures and that concordance with clinical judgment is improved by employing diagnostic algorithms. The concepts of diagnosis and 'demoralization' are discussed, and the history of screening instruments is reviewed. It is suggested that, while 'demoralization' may be a useful concept for clinicians, it poses serious drawbacks for epidemiological research because of the assumptions it involves about etiology and outcome.

Affective Symptoms↗
PubMed1985

Release of endogenous dopamine, 3,4-dihydroxyphenylacetic acid, and amino acid transmitters from rat striatal slices.

The release of endogenous dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) was measured in superfused striatal slices of the rat and the results compared with data obtained for the release of endogenous (a) DA and DOPAC in the cerebral cortex, nucleus accumbens and thalamus; (b) 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), GABA, and glutamate in the striatum; and (c) GABA, glutamate and 5-HT in the cerebral cortex. In superfused slices of all four CNS regions, there appeared to be a Ca2+-dependent, K+-stimulated release of endogenous DA. In addition, in slices of the striatum and nucleus accumbens there also appeared to be a Ca2+ -dependent, 60 mM K+ stimulated release of endogenous DOPAC. In the striatum, 16 mM Mg2+ was as effective as 2.5 mM Ca2+ in promoting the 60 mM K+-stimulated release of DOPAC. In addition, 16 mM Mg2+ appeared to function as a weak Ca2+ agonist since it also promoted the release of DA to approximately 40% of the level attained with Ca2+ in the presence of 60 mM K+. On the other hand, in the striatum, 16 mM Mg2+ inhibited the Ca2+-dependent, 60 mM K+-stimulated release of GABA and glutamate. Similar Mg2+-inhibition was observed in the cerebral cortex not only for GABA and glutamate but also for DA and 5-HT. With the use of alpha-methyl rho-tyrosine (tyrosine hydroxylase inhibitor), cocaine (uptake inhibitor) and pargyline (monoamine oxidase inhibitor), it was determined that most of the released DA and DOPAC was synthesized in the slices during the superfusion; DOPAC was not formed from DA which had been released and taken up; and DA and DOPAC were released from DA nerve terminals. In addition, the data indicate a difference in the release process between the amino acids and the monoamines from striatal slices since Mg2+ inhibited the Ca2+-dependent, K+-stimulated release of GABA and glutamate and appeared to promote the release of DA and 5-HT.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Effects of 250 mg% ethanol on monoamine and amino acid release from rat striatal slices.

A single IP injection of 2.5 g ethanol/kg body weight into the rat increased the striatal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) one hour later to 133 and 141% of control values, respectively. Blood alcohol concentrations at this time were approximately 250 mg%. The increased striatal tissue levels of DOPAC and HVA found after IP administration did not appear to be due to a direct effect of ethanol on the efflux of these two metabolites or on the release of dopamine (DA) since in vitro studies with striatal slices demonstrated that 250 mg% ethanol had no effect on the endogenous release of DOPAC, HVA, or DA. However, ethanol did enhance the K+-stimulated, Ca2+-dependent release of glutamate and aspartate from striatal slices to 168 and 214% of control values, respectively. The release of glutamate and aspartate from slices of midbrain (minus colliculi) was also increased by 250 mg% ethanol. On the other hand, the release of GABA, NE and 5-HT did not appear to be significantly altered by 250 mg% ethanol. The in vitro findings have led to the hypothesis that the elevated DOPAC and HVA levels observed in the striatum following an acute IP injection of 2.5 g/kg of ethanol are due to increased release of DA produced by the excitatory actions of glutamate (and/or aspartate) on dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Monoamine, amino acid and cholinergic interactions in slices of rat cerebral cortex.

Interactions of monoamine, amino acid and cholinergic transmitter systems were studied in slices of rat cerebral cortex using a superfusion procedure and measuring release of endogenous dopamine (DA), norepinephrine (NE), serotonin (5-HT), GABA, glutamate (GLU) and aspartate (ASP). Depolarizing concentrations of K+ were used to induce a Ca2+-dependent, Mg2+-inhibited release of the monoamines and amino acids. Submaximal release of the monoamines and amino acids was observed at 35 mM K+, which permitted studies of possible excitatory or inhibitory actions of the added agents. The 35 mM K+-stimulated, Ca2+-dependent release of GABA was inhibited 40, 30 and 25% by 100 microM NE, DA and 5-HT, respectively. The release of GLU was potentiated by NE and reduced by DA. Both DA and 5-HT inhibited the release of ASP. The Ca2+-dependent, K+-stimulated release of endogenous NE, DA and 5-HT was not altered by 100 microM GABA, GLU or ASP. However, 100 microM GLU did enhance the stimulated release of GABA. The cholinergic agonist, carbachol, enhanced the stimulated release of NE, 5-HT and GLU 10, 60 and 40%, respectively. On the other hand, carbachol attenuated the release of DA and GABA approximately 20%. One interpretation of the data is that the amino acid transmitter pathways in slices of the cerebral cortex of the rat can be controlled by monoaminergic and cholinergic systems while the monoamine afferents appear to have a cholinergic regulation but not a major direct amino acid transmitter influence.

Amino Acids↗
PubMed1985

Computer diagnosis of depression and anxiety: the Stirling County Study.

A computer programme (DPAX) was constructed for a longitudinal study of psychiatric epidemiology in Stirling County (Canada). It identifies disorders involving the syndromes of depression and anxiety based on responses given in structured questionnaire interviews. The programme follows a diagnostic algorithm that uses criteria for: (1) essential features; (2) number, frequency, and pattern of associated symptoms; (3) impairment; and (4) duration. The programme reproduces case evaluations provided by psychiatrists, as conveyed by a sensitivity of 92% and a specificity of 98%.

Anxiety Disorders↗
PubMed1984

Reassessment of the relationship of perinatal risk factors and child abuse.

We performed a case-control study to examine the relationship of child abuse to several perinatal risk factors. Cases were children who had been born at Yale-New Haven (Conn) Hospital and were reported for physical abuse to the Hospital's Child Abuse Committee. For each case, a control was chosen from the hospital's log of births and matched according to five demographic variables. We identified 117 case-control pairs. No relationship was found between either prematurity or low birth weight and child abuse. In contrast, there was an association between child abuse and young maternal age (both at the birth of the index child and at the birth of the first child). We conclude that prematurity and low birth weight are not risk factors for physical abuse but that young maternal age is related to abuse.

Adolescent↗
PubMed1984

Stability of prevalence. Depression and anxiety disorders.

Information about point prevalence of depression and anxiety disorders from two cross-sectional surveys in Stirling County (Canada) indicates that an overall prevalence rate of 12.5% characterized a year close to midcentury and a prevalence rate of 12.7% characterized another year toward the end of the century's third quarter. The stability of the prevalence rates contrasts sharply with the fact that numerous social changes took place over this period of time in this place of study. There were, however, small trends in the distribution of depression and anxiety by sex and age, especially an increased similarity in the overall rates for men and women in the age range of 40 to 69 years. Hypotheses are offered about social circumstances that may have influenced the diminishing difference between the sexes.

Adolescent↗
PubMed1984

Adenine metabolism in rat skeletal muscle.

Electrical stimulation, as anticipated brought about a fall in total ATP. Despite this there was little extra utilization of [8-14C]adenine to replace the ATP lost. The results suggest that allopurinol increased [8-14C]adenine utilization in both resting and stimulated muscle and, in particular, increased incorporation into ATP. After 30 minutes recovery total ATP levels had not returned to control resting values. [8-14C]adenine utilization, however, was markedly increased with most of the label incorporated into ATP. The results again suggest that addition of allopurinol to the medium increased [8-14C] adenine utilization of the label by recovering muscle.

Adenine↗
PubMed1984

Factors influencing first-year medical students' perceptions of stress.

This preliminary report from an ongoing longitudinal study of students at both Tufts and Harvard medical schools examined the relationship between premedical school demographic and stress variables and the numbers and types of stresses reported by students in open-ended interviews conducted during their first year of medical school. Analyses showed that the general categories of "medical school stresses" and "social stresses related to medical school" accounted for about two-thirds of the total number of stresses mentioned. The overall distributions of stresses across general categories were remarkably similar in all student groups studied, although significant differences were found between students from different background groups on a number of the specific types of stress. No significant differences were found between groups as to those reporting a high total number of stresses. There did appear to be differences in the degree to which students felt affected by the stresses they reported, suggesting the need for additional data on the meanings of different stresses for different students and the ways in which they cope with them.

Adult↗
PubMed1984

Major tranquilizer usage in psychiatric patients at Veterans Administration treatment facilities.

Three comprehensive surveys of psychiatric drug usage in Veterans Administration (VA) treatment settings, including psychiatric wards of VA hospitals, outpatient or ambulatory programs, and chronic care facilities, show thioridazine to be the most widely prescribed major tranquilizer. Among 28,323 psychiatric patients with orders for major tranquilizers, 7,719 (27.3%) had prescriptions for thioridazine. In domiciliaries and nursing homes, where patients more advanced in age are treated, 43.8% of orders for major tranquilizers were for thioridazine. Concomitant prescription of antiparkinsonian drugs was considerably less frequent with thioridazine, with only 8.7% of patients receiving such agents as compared with up to 42.5% of patients with orders for other major tranquilizers.

Aged↗