A mental exercise to fight frustration.
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Attitude of Health Personnel↗
Biomedical subjects
L H Parsons
Publications and source records attributed to L H Parsons.
D3 receptor test in vitro predicts decreased cocaine self-administration in rats.
The three dopamine agonists with highest reported D3 receptor selectivity in vitro, pramipexole, quinelorane and PD128,907, decreased self-administration of a high dose of cocaine in rats as a result of a leftward shift in the cocaine dose-effect function. In contrast the D3 preferring antagonist nafadotride increased cocaine self-administration. Moreover the relative potencies of these and other D2-like dopamine agonists (lisuride, 7-OH-DPAT, quinpirole, apomorphine, bromocriptine) to modulate cocaine self-administration were highly correlated with their relative potencies for increasing mitogenesis in vitro in cell lines expressing D3 but not D2 receptors. These results support the hypothesis that the D3 receptor may be an important target for pharmacotherapies for cocaine abuse and dependence.
Animals↗
Family violence issues in obstetrics and gynecology, primary care, and nursing texts.
OBJECTIVE: To evaluate major texts in obstetrics and gynecology, primary care, and nursing for their content in the area of family violence. METHODS: The study included 48 medical texts and 19 nursing texts published between 1990 and 1996. Key words and phrases were identified and indices searched. Minimum requirements for content on domestic violence included 12 issues identified as important. If the text contained any information on an issue, it received one point. A domestic violence content score was calculated, and a maximum score of 12 was possible. Textbooks were evaluated for content related to domestic violence as well as rape, child sexual abuse, abuse in pregnancy, and elder abuse. RESULTS: Thirty-seven percent of physician texts and 63% of nursing texts included some content on domestic violence. On our domestic violence content scale, 16% of medicine texts and 10% of nursing texts scored 9-12. CONCLUSION: The availability of information on family violence is limited in both medical and nursing texts.
Domestic Violence↗
Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission.
The mouse mutant coloboma (Cm/+), which exhibits profound spontaneous hyperactivity and bears a deletion mutation on chromosome 2, including the gene encoding synaptosomal protein SNAP-25, has been proposed to model aspects of attention-deficit hyperactivity disorder. Increasing evidence suggests a crucial role for SNAP-25 in the release of both classical neurotransmitters and neuropeptides. In the present study, we compared the release of specific neurotransmitters in vitro from synaptosomes and slices of selected brain regions from Cm/+ mice with that of +/+ mice. The release of dopamine (DA) and serotonin (5-HT) from striatum, and of arginine vasopressin and corticotropin-releasing factor from hypothalamus and amygdala is calcium-dependent. Glutamate release from and content in cortical synaptosomes of Cm/+ mice are greatly reduced, which might contribute to the learning deficits in these mutants. In dorsal striatum of Cm/+ mutants, but not ventral striatum, KCl-induced release of DA is completely blocked and that of 5-HT is significantly attenuated, suggesting that striatal DA and 5-HT deficiencies may be involved in hyperactivity. Further, although acetylcholine failed to induce hypothalamic corticotropin-releasing factor release from Cm/+ slices, restraint stress increased plasma corticosterone levels in Cm/+ mice to a significantly higher level than in +/+ mice, suggesting an important role for arginine vasopressin in hypothalamic-pituitary-adrenal axis activation. These results suggest that reduced SNAP-25 expression may contribute to a region-specific and neurotransmitter-specific deficiency in neurotransmitter release.
Acetylcholine↗
Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats.
Basal forebrain dopamine (DA) and 5-HT neurotransmission has been implicated in the mediation of the acute reinforcing actions of ethanol. Neuroadaptation theories predict that compensatory changes in neurochemical systems that are activated by alcohol acutely may underlie symptoms of withdrawal after chronic administration. To test this hypothesis, the release of DA and 5-HT was monitored by microdialysis in the nucleus accumbens of dependent male Wistar rats at the end of a 3-5 week ethanol (8.7% w/v) liquid diet regimen, during 8 hr of withdrawal, and during renewed availability of ethanol involving (1) the opportunity to operantly self-administer ethanol (10% w/v) for 60 min, followed by (2) unlimited access to the ethanol-liquid diet. Results were compared to control groups pair-fed with ethanol-free liquid diet and trained to self-administer either ethanol or water. In nondependent rats, operant ethanol self-administration increased both DA and 5-HT release in the NAC. Withdrawal from the chronic ethanol diet produced a progressive suppression in the release of these transmitters over the 8 hr withdrawal period. Self-administration of ethanol reinstated and maintained DA release at prewithdrawal levels but failed to completely restore 5-HT efflux. 5-HT levels recovered rapidly, however, within 1 hr of reexposure to ethanol liquid diet. These findings suggest that deficits in accumbal monoamine release may contribute to the negative affective consequences ethanol withdrawal and, thereby, motivate ethanol-seeking behavior in dependent subjects.
Animals↗
Serotonin1b receptor stimulation enhances dopamine-mediated reinforcement.
The effect of 5-HT1B receptor stimulation on dopamine-mediated reinforcement in rats was investigated using intravenous self-administration of the selective dopamine uptake inhibitor GBR-12909 on an FR5 schedule of reinforcement. Pretreatment with the 5-HT1A/1B receptor agonist CGS-12066B (1-10 mg/kg, IP) dose-dependently reduced the self-administration of GBR-12909 (83 micrograms/injection) by increasing the interval between drug injections, consistent with a enhancement of the reinforcing effects of GBR-12909. Additionally, CGS-12066B pretreatment (3 mg/kg, IP) shifted the dose-effect function for GBR-12909 self-administration to the left. Pretreatment with the selective 5-HT1A receptor agonist 8-OH-DPAT (0.03-1.0 mg/kg, SC) had no significant effect on GBR-12909 self-administration (83 micrograms/injection), indicating that the effect of CGS-12066B is not mediated by the 5-HT1A receptor. Finally, CGS-12066B pretreatment (1-10 mg/kg, IP) did not alter the self-administration of cocaine (0.03-0.5 mg/injection), suggesting that the simultaneous stimulation of multiple 5-HT receptor subtypes by the indirect 5-HT agonist properties of cocaine may mask the effect of 5-HT1B receptor stimulation on DA-mediated reinforcement.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Extracellular serotonin is decreased in the nucleus accumbens during withdrawal from cocaine self-administration.
Many of the withdrawal symptoms reported by human cocaine users are thought to be correlated with serotonergic dysfunction. To explore the neurochemical basis for this hypothesis, we used in vivo microdialysis to monitor extracellular serotonin (5-HT) in the nucleus accumbens of the rat both during and for several hours after unlimited-access intravenous cocaine self-administration. Self-administration of cocaine produced an increase of approx. 340% of baseline in the dialysate concentration of 5-HT that persisted for the entire 12 h session. During the first 6 h after self-administration, dialysate 5-HT levels were significantly decreased to 41% of pre-session levels and 25% of the levels in drug-naive control animals. The effects of cocaine exposure on basal extracellular 5-HT concentrations were also examined using a quantitative microdialysis method (Difference Method). Rats withdrawing from extended-access cocaine self-administration displayed significantly lower extracellular 5-HT levels (0.6 +/- 0.3 nM) than either drug-naive control animals (2.0 +/- 0.5 nM) or animals which received daily 3-h self-administration training sessions only (limited-access; 1.4 +/- 0.2 nM). Together these results indicate that extracellular 5-HT is significantly decreased in the nucleus accumbens during withdrawal from cocaine self-administration. The severity of this decrease is contingent on the length of time cocaine is self-administered.
Animals↗
Neurochemical evidence that postsynaptic nucleus accumbens D3 receptor stimulation enhances cocaine reinforcement.
The mechanism by which two D3 receptor-preferring agonists, 7-hydroxydipropylaminotetralin (7-OH-DPAT) and quinelorane, modulate cocaine reinforcement was examined by monitoring nucleus accumbens dopamine levels with in vivo microdialysis while rats intravenously self-administered the following four different drug solutions consecutively: (1) cocaine; (2) a combination of cocaine plus a low dose of either agonist; (3) either agonist alone; and finally, (4) a physiological saline solution. Both 7-OH-DPAT (4 micrograms/infusion) and quinelorane (0.25 microgram/infusion) decreased cocaine (0.25 mg/infusion) intake in a manner indicating an enhancement of cocaine reinforcement and simultaneously decreased the cocaine-induced elevations in nucleus accumbens dopamine levels by > 50%. Subsequent self-administration of either 7-OH-DPAT (4 micrograms/infusion) or quinelorane (0.25 microgram/infusion) alone resulted in significant, but stable, increases in drug intake, with a concurrent decrease in nucleus accumbens dopamine levels to approximately 50% below nondrug baseline levels. These findings indicate that postsynaptic D3 receptor stimulation in the nucleus accumbens enhances the reinforcing properties of cocaine. In a second experiment, local application of 7-OH-DPAT via reverse dialysis (30 and 100 nM perfusate concentrations) dose-dependently decreased nucleus accumbens dopamine efflux to 76 +/- 3.9 and 61 +/- 6.3% of baseline, respectively, whereas there was no effect of this agonist on dopamine efflux in the ipsilateral striatum of these same animals. Coperfusion with the D3 receptor-preferring antagonist nafadotride dose-dependently blocked the effect of 7-OH-DPAT on nucleus accumbens dopamine efflux. These results suggest that, at low concentrations, 7-OH-DPAT selectively activates D3 receptors in vivo.
Animals↗
Suppression of psychoactive effects of cocaine by active immunization.
Cocaine is a powerfully addictive substance and new strategies are needed to treat its abuse. Generating an active immunization to cocaine offers a means of blocking the actions of the drug by preventing it from entering the central nervous system, and should have fewer side effects than treatments based on manipulation of central neurotransmitter function. The design and preparation of a cocaine immunogen requires special regard for the stability of cocaine both free and as a haptenic determinant. Immunochemistry and a well defined behavioural model were brought together to address the problem of inactivation of the psychostimulant actions of cocaine. We report here that active immunization with a new, stable cocaine conjugate suppressed locomotor activity and stereotyped behaviour in rats induced by cocaine but not by amphetamine. Moreover, following acute injection of cocaine, levels of cocaine in the striatum and cerebellum of the immunized animals were lower than those of control animals. These results suggest that immunopharmacotherapy may be a promising means by which to explore new treatments for cocaine abuse.
Animals↗
Methods of and attitudes toward screening obstetrics and gynecology patients for domestic violence.
OBJECTIVE: Our purpose was to define screening behaviors of obstetrician-gynecologists and barriers to screening their patients for domestic violence. STUDY DESIGN: A questionnaire was developed to collect information on current practices and attitudes regarding screening for domestic violence. A randomly selected sample of obstetrician-gynecologists was surveyed. Respondents were also asked to rank a series of 19 potential barriers that may affect screening. RESULTS: Of 6568 physicians sampled, 962 (14.6%) returned questionnaires. Of the respondents, 77.6% were male and 22.4% were female. Male physicians were less likely to screen for domestic violence (25.9% vs. 18.9%). Thirty-four percent said that they had no training in abuse. Physicians indicating they had received training in abuse were more likely to screen for domestic violence. The lack of education was identified as the most common barrier physicians have to screening. The feeling that abuse was not a problem in their patients (46%), lack of time to deal with abuse (39.2%), and frustration that the physician cannot help the victim (34.2%) were other common barriers. CONCLUSION: The majority of obstetrician-gynecologists do not screen their patients for current or past domestic violence. If universal screening is to become a reality, educational tools and training materials are needed to overcome physician barriers.
Adult↗
Synthetic hygroscopic cervical dilator use in patients with unsatisfactory colposcopy.
OBJECTIVE: To assess the ability of a synthetic hygroscopic cervical dilator to make an unsatisfactory colposcopic examination satisfactory, thereby avoiding cervical conization. MATERIALS: From April 1991 to March 1993, 30 women with unsatisfactory colposcopic examinations underwent repeat colposcopy after a synthetic hygroscopic cervical dilator had been placed in the endocervical canal for approximately 2 hours. RESULTS: The reasons for initial unsatisfactory colposcopy in the 30 patients were squamocolumnar junction not seen in its entirety (18 patients, 60%), lesion not seen in its entirety (ten, 33%), and neither transformation zone nor lesion seen in their entirety (two, 7%). Complications were encountered in one patient from whom the dilator could not be removed completely. Of 29 patients undergoing repeat colposcopy, 23 (79%) had satisfactory examinations. In 15 of 30 patients, conization was avoided; it was required in six of 30 (20%) women for persistent unsatisfactory colposcopy (including the patient in whom the dilator broke) and in nine of 30 (30%) for other indications. CONCLUSIONS: This experience suggests that a synthetic hygroscopic cervical dilator can be used in patients with an unsatisfactory colposcopy to achieve a satisfactory examination, thus avoiding cervical conization.
Abortifacient Agents↗
Compliance with return appointments for reproductive health care among adolescent Norplant users.
PURPOSE: Norplant's long duration of action may result in users being less motivated than non-users to return for reproductive health care appointments. This study determined compliance with scheduled return appointments among adolescents using Norplant and those using other methods of contraception. METHODS: We retrospectively reviewed the records of all teenagers (age < or = 18 years) who received Norplant between June 1991 and August 1993, as well as those of a comparison group of adolescents, matched for age and race, using other methods of contraception. Subjects receiving Norplant were given appointments for a two-week and an annual examination. Comparison subjects were given only an appointment for an annual examination. Norplant users not returning within 5 weeks or any subject not presenting within 12 months for an annual examination, were considered non-compliant. RESULTS: Eighty-eight adolescents received Norplant during the study period and the records of 85 were available for review. Only 48 of the 85 Norplant users returned for scheduled two-week check-up, while 18 of 43 subjects who had Norplant at least 12 months were compliant with annual examinations. The compliance rate with annual examinations among the 89 subjects not using Norplant was 38%, not dissimilar from that of the Norplant group. CONCLUSIONS: These data demonstrate that compliance with return appointments for reproductive health care among adolescent Norplant users is poor but not significantly worse than that of non-users of Norplant. Strategies promoting the benefits of return visits need to be improved for adolescents receiving contraception.
Adolescent↗
Identification of male epithelial cells in routine postcoital cervicovaginal smears using fluorescence in situ hybridization. Application in sexual assault and molestation.
In a prospective blinded controlled study, the efficacy of fluorescence in situ hybridization (FISH) to detect non-sperm male cells verifying sexual contact was examined. Cervicovaginal smears (CVS) from 40 women with reported post-coital intervals were examined for sperm by cytology and for sperm and non-sperm male cells by FISH using X and Y chromosome specific DNA probes. Fluorescence in situ hybridization identified sperm and/or non-sperm male cells in all specimens from women with positive coital histories, including when the partner had a vasectomy. Male cells were also detectable by FISH in CVS up to 3 weeks after coitus. In comparison, cytology identified sperm in 41% of the positive coital history cases, and none beyond 2 weeks. Fluorescence in situ hybridization is highly sensitive and specific in detecting male cells, and can be performed rapidly on routine CVS. Application of this technique can provide new and additional evidence of sexual contact when current tests are inconclusive.
Coitus↗
Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine.
To test the hypothesis that cocaine withdrawal is associated with abnormalities in serotonin (5-HT) neurotransmission, 5-HT concentrations in the nucleus accumbens (NAC) of rats were analyzed with microdialysis both during and after 12 h of unlimited-access intravenous cocaine self-administration. For comparison with previous work, dopamine (DA) levels were also monitored. Self-administration produced sustained increases of both 5-HT and DA to approximately 340% of base line. During the first 6 h of withdrawal, dialysate 5-HT concentrations decreased to 41% of base-line levels obtained before self-administration and to 25% of levels in drug-naive control animals. During the same period, dialysate DA decreased to 72% of presession base-line concentrations but did not decline below control levels. Extracellular 5-HT concentrations were subsequently estimated by use of a quantitative microdialysis technique. After 12 h of self-administration extracellular 5-HT levels were significantly lower (0.6 +/- 0.3 nM) than levels in drug-naive animals (2.0 +/- 0.5 nM) or in rats given only limited-access to cocaine (3 h/day; 1.4 +/- 0.2 nM). Additionally, after 12 h of self-administration low concentrations of intra-accumbens 5-HT applied by reverse dialysis significantly elevated DA efflux. This effect was not observed in either control animals or in rats given only limited access to cocaine. These results suggest that deficient 5-HT neurotransmission may be a significant factor in the cocaine withdrawal symptomatology and provide key information regarding nondopaminergic mechanisms involved in cocaine dependence.
Animals↗
Effect of tetrodotoxin and potassium infusion on microdialysis extraction fraction and extracellular dopamine in the nucleus accumbens.
The effects of tetrodotoxin (TTX) and K+ perfusion on extracellular DA concentration (DAext) and extraction fraction (also known as relative recovery or Ed) were studied using a method for quantitative microdialysis under transient conditions. TTX administered through the microdialysis probe decreased DAext with no effect on Ed. Perfusion with high K+ increased DAext, with no initial effect on Ed. However, a decrease in Ed was observed under prolonged depolarization. These data provide further evidence that Ed may change over the course of drug administration. This method of quantitative microdialysis is a reliable means for measuring changes in DAext independently of possible changes in microdialysis probe efficiency.
Animals↗
Quantitative approaches to in vivo brain microdialysis.
The microdialysis technique has been widely used for the study of extracellular chemical events in various tissues. Until recently, however, little was known about the sampling characteristics of dialysis probes in vivo. The purpose of this review is to describe several theoretical models of in vivo microdialysis that consider both the diffusional resistances encountered in vivo and the effects of various active processes, such as metabolism, release and uptake, and transport across the blood brain barrier. The relevance of the models to practical in vivo microdialysis experiments is discussed. Several microdialysis techniques that quantitatively estimate extracellular analyte concentrations are also reviewed. These techniques are discussed in relation to the theoretical models, together with a discussion of the experimental factors that affect in vivo microdialysis experiments.
Animals↗
Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis.
The effects of local application of serotonin (5-HT) on extracellular levels of dopamine (DA) in the nucleus accumbens (N. ACC) were assessed using in vivo microdialysis. At a perfusate flow rate of 0.3 microliter/min the baseline dialysate concentration of DA was 2.1 +/- 0.7 nM (mean +/- S.E.M.; n = 5) and significantly increased to 142 +/- 18%, 220 +/- 47% and 332 +/- 35% of baseline when 0.1 microM, 0.2 microM and 0.4 microM concentrations of 5-HT were included in the perfusate. Perfusate 5-HT concentrations below 0.1 microM had no effect on dialysate DA. The in vivo dialysis efficiency for 5-HT was found to be 39 +/- 12%, and thus the concentrations of 5-HT reaching the extracellular space at the surface of the dialysis membrane were estimated to be 40, 80 and 160 nM for the 0.1, 0.2 and 0.4 microM 5-HT perfusates, respectively. The serotonin-induced increase in dialysate DA was attenuated by co-perfusion of 0.4 microM 5-HT with 4 microM concentrations of pindolol (a relatively non-specific 5-HT1 antagonist; 151 +/- 7% vs. 332 +/- 35% baseline dialysate DA for 5-HT/antagonist and 5-HT-only perfusates, respectively), LY 53,857 (a specific 5-HT2 antagonist; 130 +/- 17% vs. 332 +/- 35%) and MDL 7222 (a specific 5-HT3 antagonist; 143 +/- 19% vs. 332 +/- 35%).(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dihydroxyphenylacetic Acid↗
Co-administration of the D2 antagonist pimozide inhibits up-regulation of dopamine release and uptake induced by repeated cocaine.
To investigate the hypothesis that the D2 dopamine (DA) receptor regulates DA uptake, as well as release, in the nucleus accumbens (N ACC), rats were pretreated for 10 days with either the selective D2 antagonist pimozide (1.0 mg/kg, i.p.) or vehicle, followed 3 h later by either cocaine (20 mg/kg, i.p.) or saline. On day 11, a microdialysis method was performed in which various DA concentrations (0, 10, and 20 nM DA) were perfused through the dialysis probe to characterize the diffusion of DA through tissue to and from the microdialysis probe (recovery). This diffusion of DA has been shown to be sensitive to changes in release and uptake. Pimozide pretreatment was shown to attenuate significantly a cocaine-induced increase in the in vivo recovery of DA (p < 0.01). The in vivo recovery for the vehicle/cocaine group was 47 +/- 4%, whereas the in vivo recovery for the pimozide/cocaine group was 31 +/- 3%. There was no difference between the pimozide/cocaine and control groups (pimozide/saline, 26 +/- 2%; vehicle/saline, 26 +/- 3%). In vitro probe calibrations indicated no significant difference in probe efficiencies between groups. These data suggest that the D2 receptor is capable of modulating uptake as well as release of DA in the N ACC of the rat.
Analysis of Variance↗