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Biomedical subjects

J M Murphy

Publications and source records attributed to J M Murphy.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Biochemical evidence for activation of specific monoamine pathways by ethanol.

The effects of an acute intraperitoneal (IP) low (0.5 g/kg) or high (2.5 g/kg) dose of ethanol on the contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in 7 selected CNS regions of the rat were examined after 15, 30 and 60 minutes. The IP administration of 0.5 g/kg ethanol produced blood alcohol concentrations (BACs) of 41 +/- 4, 40 +/- 4 and 15 +/- 1 mg% (N = 8 each) after 15, 30 and 60 minutes, respectively. This low dose of ethanol did not alter the levels of DA, DOPAC, HVA, 5-HT and 5-HIAA in any of the 7 CNS regions at any of the time points examined. The dose of 2.5 g/kg ethanol produced BACs of 254 +/- 26, 268 +/- 20 and 282 +/- 10 mg% (N = 8 each) after 15, 30 and 60 minutes, respectively. This high dose of ethanol did not alter the contents of DA and 5-HT in any of the regions examined at any of the times, except for a 30% increase in the content of DA in the posterior striatum after 60 minutes. The administration of 2.5 g ethanol/kg elevated the levels of DOPAC and/or HVA 25 to 70% over saline control values in the (a) nucleus accumbens (ACC) and hypothalamus (HYPO) after 15, 30 and 60 minutes, and (b) posterior striatum (PSTR), lateral septal nucleus (LSN) and frontal cortex (FCTX) after 60 minutes. The contents of DOPAC and/or HVA were not altered by the high dose of ethanol in either the thalamus or olfactory bulbs.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Operant responding for oral ethanol in the alcohol-preferring P and alcohol-nonpreferring NP lines of rats.

Rats of the P (n = 4) and NP (n = 5) lines were housed in operant chambers with food available ad lib, but all liquid was obtained by responding on either of two levers according to a FR5 schedule. Presses on one lever produced water from an automated dipper, while the other lever gave access to a dipper containing ethanol in concentrations ranging from 2 to 30% (v/v). P rats worked to obtain the ethanol at all concentrations offered and preferred the ethanol over water. The highest ethanol intake averaged 7.7 +/- 0.5 g/kg body weight/day at the 15% concentration and at least 5.8 +/- 0.9 g/kg/day for the 20-30% range. The NP rats responded more for the 2 and 5% concentrations of ethanol than for water, but responded predominantly for water when the ethanol concentrations were 10% and higher. In a second experiment, NP rats drank water rather than 10% ethanol by free-choice, even though the ethanol was mixed with a preferred flavor and the water with a nonpreferred flavor. The findings indicate that ethanol is rewarding to P rats in concentrations up to 30% (v/v) but is not rewarding to NP rats when the concentration is 10% and above.

Alcohol Drinking↗
PubMedDate not supplied

Regional brain contents of serotonin, dopamine and their metabolites in the selectively bred high- and low-alcohol drinking lines of rats.

The contents of dopamine (DA), serotonin (5-HT) and their primary acid metabolites were assayed in ten brain regions of the selectively bred high-alcohol drinking (HAD) and low-alcohol drinking (LAD) lines of rats. Compared with the LAD line, the contents of 5-HT and/or 5-hydroxyindoleacetic acid were approximately 10-20% (p less than 0.05) lower in several brain regions of the HAD line (cerebral cortex, striatum, nucleus accumbens, septal nuclei, hippocampus and hypothalamus). The levels of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid were also 10-20% lower in the nucleus accumbens and anterior striatum (p less than 0.05) of the HAD animals. These data are in agreement with previous findings that comparatively lower levels in 5-HT and DA systems are associated with high-alcohol drinking in rodents and support the involvement of certain 5-HT and DA pathways in the mediation of alcohol drinking behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats.

Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT), dopamine (DA) and GABA systems in regulating the alcohol-drinking behavior of two lines of rats selectively bred for their high alcohol-seeking behavior, namely the alcohol-preferring P line and the high alcohol-drinking HAD line of rats. Neurochemical data indicate that high alcohol-seeking behavior (when compared with data from rats with low alcohol-seeking characteristics) is associated with: a) lower (10-20%; p less than 0.05) contents of 5-HT in certain limbic regions (e.g., nucleus accumbens, frontal cortex, hypothalamus and hippocampus); b) a lower (10-15%; p less than 0.05) content of DA in the nucleus accumbens; c) higher (20-35%; p less than 0.05) densities of 5-HT1A binding sites in some limbic regions (e.g., medial nucleus accumbens, medial prefrontal cortex and ventral hippocampus); and d) a greater (20-50%) density of GABA axon terminals in the nucleus accumbens. Furthermore, the acute administration of high doses of ethanol appears to increase the activity of the 5-HT and DA projections to the nucleus accumbens of the P line of rats (as indicated by the 20-30% elevated tissue levels of 5-HT and DA metabolites following IP ethanol administration); neuronal tolerance to alcohol appears to develop in both these monoamine pathways, as suggested by an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

Effects of fluoxetine and desipramine on palatability-induced ethanol consumption in the alcohol-nonpreferring (NP) line of rats.

Three groups of NP rats (n = 5/group) received food, water and one of 3 Polycose solutions ad lib. One group received a solution containing 3% (w/v) Polycose, 0.125% (w/v) saccharin, 0.5% (w/v) NaCl (3% POL solution) to which ethanol was gradually added over three weeks until the concentration of 10% (v/v) ethanol (E) was reached (3% POL + E group). Alcohol ingestion by the 3% POL + E group reached an average of 9 g of ethanol/kg b. wt./day; the rats attained average blood alcohol concentrations of 61 +/- 8 mg%. One control group (3% POL) was given the same solution as above but without ethanol. The second control group (17% POL) had access to a 17.6% Polycose solution supplemented with 0.125% saccharin and 0.5% NaCl and was isocaloric to the 3% POL + E solution. Although the three groups differed significantly in the amounts of food and Polycose solutions consumed, their total caloric intakes were equivalent. The IP administration of the serotonin (5-HT) uptake inhibitor fluoxetine (5 and 10 mg/kg) significantly reduced drinking of the group receiving the 3% POL + E solution by 23% and 67%, respectively, but did not alter intakes of the Polycose solutions by the 3% or 17% POL control groups. The IP administration of the norepinephrine (NE) uptake inhibitor desipramine (5 and 10 mg/kg) significantly reduced intake of the Polycose solution by the 17% POL group by 52 and 83%, respectively, but only the 10 mg/kg dose attenuated drinking of the solutions by the 3% POL and 3% POL + E groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

Persistence of tolerance in the P line of alcohol-preferring rats does not require performance while intoxicated.

Persistence of tolerance was measured seven days after a single ethanol injection (2.5 g/kg b. wt.) in the alcohol-preferring P line of rats with and without testing in a shock-motivated jump task during the initial ethanol exposure. P rats were trained to jump 50 cm to avoid shock and were assigned to one of three groups. On day 0, group E/J (n = 8) was injected with ethanol and tested on the jump task until recovery to criterion (37.5 cm), while group S/J (n = 21) was injected with saline and was tested yoked to an E/J rat. Rats in the E/NJ group (n = 19) received ethanol but were not tested on day 0. Seven days later, all rats received 2.5 g ethanol/kg and were tested to criterion. Recovery times on day 7 were significantly longer (p less than 0.05) for rats in the S/J group (169 +/- 7 min) than for the E/J (141 +/- 11 min) and E/NJ (145 +/- 6 min) rats. Blood ethanol concentrations at recovery for the E/NJ group were higher than the S/J group on day 7 and higher than the E/J group on day 0 (p less than 0.05). The results indicate that the persistence of tolerance manifested by the P rats is an inherited behavioral trait that requires only ethanol exposure.

Alcohol Drinking↗
PubMedDate not supplied

Effects of D1 and D2 dopamine receptor agents on ethanol consumption in the high-alcohol-drinking (HAD) line of rats.

Dopamine receptor agonists and antagonists were tested for effects on alcohol drinking in female HAD rats (n = 10) given limited access (4 h/day) to a 10% (v/v) ethanol solution. Food and water were available ad libitum. Subcutaneous drug injections were given 30-60 min before the ethanol access periods. The D2 agonist quinpirole (0.04-2.0 mg/kg) caused a dose-dependent decrease in alcohol drinking throughout the 4-h period. Spiperone, a D2 antagonist, had no effect during the initial part of the session, but by the fourth hour, the 10 micrograms/kg dose tended to increase alcohol intake and the 30 micrograms/kg dose reduced intake. The D1 antagonist SCH-23390 (3-30 micrograms/kg) dose-dependently decreased ethanol drinking during the first hour of access. The D1 agonist SKF-38393 (2-6 mg/kg) also decreased alcohol intake, but it was less effective than SCH-23390. The findings implicate both D1 and D2 receptors in the reinforcing effects of alcohol drinking by the HAD line of rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMedDate not supplied

Comparison of alcohol-preferring (P) and nonpreferring (NP) rats on tests of anxiety and for the anxiolytic effects of ethanol.

Rats of the selectively bred alcohol-preferring P and alcohol-nonpreferring NP lines were evaluated using three different behavioral measures of anxiety. Compared with NP rats, P rats (1) showed greater footshock-induced suppression of operant responding in an approach-avoidance conflict test; (2) spent less time in the open arms of an elevated plus maze; and (3) took longer in a passive avoidance test to step down from a platform to a grid floor where footshock was received 24 hours earlier. These findings indicate a greater degree of anxiety in the P than in the NP line of rats in these situations. Pretreatment with intraperitoneal (IP) ethanol (0.5-1.0 g/kg) injections produced anticonflict or anxiolytic effects in P but not in NP rats. However, the anticonflict effects of ethanol were small relative to those produced by chlordiazepoxide (CDP, 7.5 mg/kg) in both lines. The results demonstrate that selective breeding for divergent oral ethanol preference has produced associated differences between the P and NP lines of rats in behavioral tests of anxiety and in the anxiolytic effects of ethanol.

Alcohol Drinking↗
PubMedDate not supplied

Ethanol self-infusion into the ventral tegmental area by alcohol-preferring rats.

The ventral tegmental area (VTA) and its projections have been implicated in the reinforcing effects of drugs of abuse. Selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines of rats were used to evaluate the reinforcing actions of ethanol in the VTA using intracranial self-administration (ICSA) operant procedures. P rats self-administered nanoliter quantities of 50-200 mg% ethanol in artificial CSF directly into the VTA whereas NP rats had low levels of responding at these ethanol concentrations. Responses on the active lever were 50-fold higher for the P compared with the NP rats for the self-infusion of 150 mg% ethanol. NP rats responded at the same level on the active and inactive levers at all ethanol concentrations and had low responses/session (3 to 15 total responses) at all concentrations. Further, operant responding on the active lever was reduced when artificial CSF alone was substituted for 100 mg% ethanol, and responding on the active lever was reinstated when ethanol was returned. For one group of rats, an illuminated house light served as a discriminative stimulus, which signalled the availability of ICSA, while a cue light was paired with the onset of ethanol infusion. Extinction in the presence of these stimuli required 6-7 sessions. However, only 2-3 extinction sessions were necessary for another group trained without stimulus cues, suggesting that cues paired with the ICSA of ethanol can acquire conditioned reinforcing properties. The findings indicate that ethanol can act as a reinforcer when administered directly into the VTA.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

Apomorphine and 7-OH DPAT reduce ethanol intake of P and HAD rats.

Adult male rats of the alcohol-preferring (P) line (N = 10) and high alcohol drinking (HAD) line (N = 12) were used to study the effects of IP administration of 0.125-0.50 mg/kg 7-OH DPAT (a putative D agonist) and 0.25-1.0 mg/kg apomorphine (a dopamine agonist with 50-fold higher affinities for the D1 and D2 receptors than for the D3 receptor) on the concurrent intakes of 10% (v/v) ethanol and 0.0125% (g/v) saccharin during a daily 4-h scheduled access period. Control intakes by the P rats for the 4-h period were 17.9 +/- 0.5 and 7.2 +/- 0.4 ml for the ethanol and saccharin solutions, respectively. For the HAD line, ethanol consumption was 18.7 +/- 0.2 ml and saccharin intake was 8.7 +/- 1.6 ml for the 4-h period. In terms of grams ethanol/kg body wt, the 4-h intakes were 2.2 +/- 0.2 for the P line and 3.0 +/- 0.3 for the HAD rats. Both P and HAD rats consumed approximately 40% of their total ethanol intake in the first 15 min of access while consuming only about 15% of their total saccharin intake during this 15-min period. The putative D3 agonist 7-OH DPAT produced a decrease in ethanol intake in the first h to 45-55% of control levels for the P rat (p < 0.01) and to 25-70% of control values in the HAD line (p < 0.001). Apomorphine caused a dose-dependent decrease in ethanol intake in the first hour to 15-70% of control values in the P rat (p < 0.001) and to 25-60% of control levels in the HAD line (p < 0.001). Saccharin and 4-h food intakes for both lines were not altered by either 7-OH DPAT or apomorphine. Overall, these results suggest that D2 and D3 dopamine receptors may play a role in mediating alcohol drinking behavior of the selectively bred HAD and P lines of rats.

Alcohol Drinking↗
PubMedDate not supplied

Long-term effects of alcohol drinking on cerebral glucose utilization in alcohol-preferring rats.

The 2-[14C]deoxyglucose (2-DG) quantitative autoradiography technique was used to determine rates of local cerebral glucose utilization (LCGU) in discrete brain regions in alcohol-chronic (A-C), alcohol-deprived (A-D) and alcohol-naïve (A-N) adult, male alcohol-preferring (P) rats. The hypothesis to be tested is that neuronal alterations occur as a result of chronic alcohol drinking and some of these alterations persist for long periods in the absence of alcohol. Following 6 weeks of daily 4-h scheduled access sessions to 15% (v/v) ethanol and water, group A-D received only water during the sessions over the next 2 weeks, whereas groups A-C and A-N continued to receive ethanol-water and water-water, respectively. On the 14th day of the deprivation interval, LCGU rates were measured 1 h prior to the scheduled access period. Mean ethanol intake for the A-D and A-C groups was 1.5+/-0.1 g ethanol/kg body weight per 4 h. LCGU rates were significantly decreased in 49 of 57 regions or subregions examined in the A-C group compared to the A-N group, including subregions of the cerebral cortex, hippocampus and structures in the mesocorticolimbic and nigrostriatal systems. Following alcohol deprivation, LCGU values in the A-D group were partially or completely returned to A-N levels in many, but not all, regions. In several limbic regions (e.g., ventral tegmental area, olfactory tubercle, medial prefrontal cortex, ventral pallidum and lateral septum), no recovery of LCGU rates was observed after 2 weeks of alcohol deprivation. This study demonstrates that chronic alcohol consumption produces significant reductions in functional neuronal activity in P rats, some of which persist in the absence of ethanol. The extent to which LCGU rates returned to normal levels following 2 weeks of alcohol deprivation varied among brain regions, suggesting that there are imbalanced interactions among and within several CNS sites, which do not reflect either the alcohol-naïve or chronic alcohol-exposed state. Such neuronal imbalances may underlie relapse of alcohol drinking following prolonged abstinence.

Alcohol Drinking↗
PubMedDate not supplied

Effects of amphetamine on locomotor activity in adult and juvenile alcohol-preferring and -nonpreferring rats.

The objective of this study was to determine whether functional differences exist in amphetamine-induced locomotor activity between alcohol-naive alcohol-preferring (P) and -nonpreferring (NP) rats during postnatal development and during adulthood. Using a between-subjects design, 20- and 28-day-old P and NP rats (male and female counterbalanced, n=11-16/line) were habituated for 30 min in a photocell activity field. Each rat received subcutaneous injections of saline or 0.3, 0.6 or 1.2 mg/kg d-amphetamine (AMPH) and were then tested for an additional 30 min. Because of age and line differences in basal locomotor activity, total activity counts during the 30-min postdrug period were standardized using Z-score transformations. In the 20- and 28-day-old rats, dose-dependent locomotor activity increases after AMPH injections were obtained at both ages, although activity levels were greater in the 20-day-old pups. The 20-day-old female NP rats showed greater AMPH-induced increases in locomotor activity than P rats, whereas at 28 days of age, male NP rats showed greater activity levels than P rats to AMPH. For the adult P and NP rats (n=8/line/gender), a within-subject design was used. In the adults, the NP line had higher locomotor activity than the P line following AMPH injection, and male rats were activated more by AMPH than female rats. The results suggest that functioning of the DA system in the adult P line is reduced compared to the adult NP line, and this line difference is also observed to some degree at an early postweaning developmental period.

Aging↗
PubMedDate not supplied

Child passenger safety.

Motor vehicle crashes are a leading cause of death and disability among children in the United States despite the fact that child safety seats and seat belts can provide effective protection against serious and fatal injuries. Many child car seats and safety restraints are being used incorrectly. In addition, recent fatalities associated with children and air bags have heightened awareness of child passenger safety issues. Pediatric nurse practitioners are in an excellent position to offer motor vehicle occupant prevention strategies to families through health education and anticipatory guidance.

Accidents, Traffic↗
PubMedDate not supplied

Depression in children after recovery from severe burns.

This outcome study of children and adolescents with severe burns (ages 7 to 19 years) reports that unrecognized depression is common during their lifetimes. Thirty children who had severe burns (range, 5% to 95% body surface area) were assessed for depression at a mean of 9 years after burn injury. This article presents an analysis of depression items from the Diagnostic Interview for Children and Adolescents, which was used in face-to-face interviews to assess child psychiatric disorders with diagnostic criteria from the American Psychiatric Association's Diagnostic and Statistical Manual--Third Edition. At the time that the interviews took place, only one child had symptoms of major depression and only three children had symptoms of dysthymic disorder. However, eight children had a lifetime history of major depression; two of them had been abused by burning and two had been physically or sexually abused. Four had made suicide attempts: one suicide attempt was the cause of the burn injury and three attempts were made after burn injury. Thirteen children had had suicidal thoughts, and their parents were often unaware of this. Other types of affective disorders were prevalent. There was no statistically significant association between depression and burn size or disfigurement. Although burn-related factors were associated with some depressive episodes, other biologic and social risk factors were also very important. The authors conclude that referral for diagnostic services and psychotherapy, and for some, treatment with antidepressant medication, is often a necessary part of medical services for children with burns.

Adolescent↗
PubMedDate not supplied

Posttraumatic stress disorder in mothers of children and adolescents with burns.

This is the first study of of posttraumatic stress symptoms in parents (24 mothers and one father) of children with burns. The purpose of the study was to determine what factors relate to parental posttraumatic stress disorder (PTSD). Because the sample is all mothers, except for one father, the conclusions are about mothers. Through use of the Structured Clinical Interview for DSM-III-R, symptoms were determined as occurring from the time of the burn injury until 1 month before the interview (past), 1 month before the interview only (present), or from the date of the burn trauma up to and including 1 month before the interview (past and present). By Structural Clinical Interview criteria, 52% of the mothers had past PTSD, with four (31%) of those mothers having present PTSD symptoms. Eleven mothers and the one father reported neither past nor present PTSD. Multiple regression analysis revealed that larger burns were more strongly related to present PTSD symptoms than were proximity, social support, or perceived stress. Additional findings indicated that mothers with more than one child burned and those mothers who were burned themselves met diagnostic criteria for PTSD. Implications are that posttraumatic stress symptoms can be disruptive to a mother feeling capable of caring for her child with burns after the injury. Individual and group therapy during and after a child's hospitalization may be useful for mothers to reduce stress and to develop better coping skills.

Adolescent↗
PubMedDate not supplied

Effects of ethanol on monoamine and amino acid release from cerebral cortical slices of the alcohol-preferring P line of rats.

The effects of 250 mg/100 ml ethanol on the efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and the 35 mM K+-stimulated, Ca2+-dependent release of norepinephrine (NE), dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate, and aspartate from cerebral cortical slices of the alcohol-preferring P line of rats and stock Wistar rats were studied. The K+-stimulated, Ca2+-dependent release of GABA for the P rats was 35% lower, while the release of glutamate was almost twice that of the stock animals. The release of the other compounds was similar for the two groups. Addition of 250 mg/100 ml ethanol to the superfusion media did not alter the release of NE, DA, and 5-HT nor the efflux of DOPAC from cortical slices of either group of rats. However, the K+-stimulated, Ca2+-dependent release of GABA, glutamate, and aspartate was significantly enhanced by ethanol for both the P and stock group of rats. These in vitro data do not support a direct action of ethanol on DA, NE, and 5-HT release or on DOPAC efflux, but suggest a direct action on the transmitter release process for GABA, glutamate, and aspartate in the cerebral cortex.

Alcohol Drinking↗
PubMedDate not supplied

Sex differences and interpersonal relationships: a cross-sectional sample in the U.S. and India.

This study introduces a methodology for exploring sex differences and life span patterns in a small sample for the purpose of generating hypotheses concerning the frequency and kinds of relationships people identify as important. Sixty-two participants from the United States and India, ranging in age from nineteen to seventy-five were interviewed as part of a study on ego and moral development. These open-ended, semistructured interviews yielded information on relationships that was subsequently coded for analysis. Sex differences were found in the number of relationships mentioned, with females mentioning a higher number of relationships than males. Life span patterns regarding the number of relationships mentioned were different for men and women between ages nineteen to thirty-one, with women naming more relationships. At age thirty-five there was a convergence in the number of relationships mentioned by both sexes. This age also was the low point in the number of relationships mentioned by both sexes, with later life ages.

Adult↗