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L H Parsons

Publications and source records attributed to L H Parsons.

At least 19 recordsLinked to original sources
PubMed2001

Functional consequences of repeated (+/-)3,4-methylenedioxymethamphetamine (MDMA) treatment in rhesus monkeys.

Six rhesus monkeys were trained to stable performance on neuropsychological tests of memory, reinforcer efficacy, reaction time and bimanual motor coordination. Three monkeys were then exposed to a high-dose, short course regimen of (+/-)3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") (4 days, 10 mg/kg i.m., b.i.d.). Following treatment, concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) were reduced by approximately 50% in the treated animals, and this effect persisted for approximately three months post-MDMA. Behavioral performance was disrupted during acute MDMA treatment but returned to baseline within one week following treatment. MDMA also produced persistent alterations in late peak latencies of brainstem auditory evoked potentials (BSAEP), lasting three months post-MDMA. Both CSF 5-HIAA concentrations and evoked potential latencies were normalized four months after treatment. These findings indicate that serotonergic alterations associated with MDMA use may result in persisting changes in brain function.

Animals↗
PubMed2001

5-HT(1A) receptor mutant mice exhibit enhanced tonic, stress-induced and fluoxetine-induced serotonergic neurotransmission.

Mutant mice that lack serotonin(1A) receptors exhibit enhanced anxiety-related behaviors, a phenotype that is hypothesized to result from impaired autoinhibitory control of midbrain serotonergic neuronal firing. Here we examined the impact of serotonin(1A) receptor deletion on forebrain serotonin neurotransmission using in vivo microdialysis in the frontal cortex and ventral hippocampus of serotonin(1A) receptor mutant and wild-type mice. Baseline dialysate serotonin levels were significantly elevated in mutant animals as compared with wild-types both in frontal cortex (mutant = 0.44 +/- 0.05 n M; wild-type = 0.28 +/- 0.03 n M) and hippocampus (mutant = 0.46 +/- 0.07 n M; wild-type = 0.27 +/- 0.04 n M). A stressor known to elicit enhanced anxiety-like behaviors in serotonin(1A) receptor mutants increased dialysate 5-HT levels in the frontal cortex of mutant mice by 144% while producing no alteration in cortical 5-HT in wild-type mice. There was no phenotypic difference in the effect of this stressor on serotonin levels in the hippocampus. Fluoxetine produced significantly greater increases in dialysate 5-HT content in serotonin(1A) receptor mutants as compared with wild-types, with two- and three-fold greater responses being observed in the hippocampus and frontal cortex, respectively. This phenotypic effect was mimicked in wild-types by pretreatment with the serotonin(1A) antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (p-MPPI). These results indicate that deletion of central serotonin(1A) receptors results in a tonic disinhibition of central serotonin neurotransmission, with a greater dysregulation of serotonin release in the frontal cortex than ventral hippocampus under conditions of stress or increased interstitial serotonin levels.

Aminopyridines↗
PubMed2000

Neurotrophic factor expression after CNS viral injury produces enhanced sensitivity to psychostimulants: potential mechanism for addiction vulnerability.

Hypothesized risk factors for psychostimulant, amphetamine, and cocaine abuse include dopamine (DA) receptor polymorphisms, HIV infection, schizophrenia, drug-induced paranoias, and movement disorders; however, the molecular, cellular, and biochemical mechanisms that predispose to drug sensitivity or drive the development of addiction are incompletely understood. Using the Borna disease rat, an animal model of viral-induced encephalopathy wherein sensitivity to the locomotor and stereotypic behavioral effects of d-amphetamine and cocaine is enhanced (Solbrig et al., 1994, 1998), we identify a specific neurotrophin expression pattern triggered by striatal viral injury that increases tyrosine hydroxylase activity, an early step in DA synthesis, to produce a phenotype of enhanced amphetamine sensitivity. The reactive neurotrophin pattern provides a molecular framework for understanding how CNS viral injury, as well as other CNS adaptations producing similar growth factor activation profiles, may influence psychostimulant sensitivity.

Animals↗
PubMed2000

Control of cocaine-seeking behavior by drug-associated stimuli in rats: effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens.

The conditioning of the pharmacological actions of cocaine with environmental stimuli is thought to be a critical factor in the long-term addictive potential of this drug. Cocaine-related stimuli may increase the likelihood of relapse by evoking drug craving, and brain-imaging studies have identified the amygdala and nucleus accumbens (NAcc) as putative neuroanatomical substrates for these effects of cocaine cues. To study the significance of environmental stimuli in the recovery of extinguished cocaine-seeking behavior, male Wistar rats were trained to associate discriminative stimuli (SDeltas) with response-contingent availability of intravenous cocaine vs. saline. The rats then were subjected to repeated extinction sessions during which cocaine, saline, and the respective SDeltas were withheld until the animals reached an extinction criterion of </=4 responses over three consecutive sessions. Subsequent re-exposure to the cocaine SDelta, but not the nonreward SDelta, produced strong recovery of responding at the previously active lever in the absence of any further drug availability. The efficacy and behavioral selectivity of the cocaine SDelta remained unaltered throughout an 8-day test period. Exposure to the cocaine SDelta significantly increased dopamine efflux in the NAcc and amygdala as measured by intracranial microdialysis in a separate group of rats. Dopamine levels remained unaltered in the presence of the nonreward SDelta. The results demonstrate that cocaine-predictive stimuli elicit robust and persistent cocaine-seeking behavior, and that this effect may involve activation of dopamine transmission in the NAcc and amygdala.

Amygdala↗
PubMed1999

RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist.

Recent studies suggest that serotonergic neurotransmission through the serotonin-1B (5-HT1B) receptor is involved in reward processes. The purpose of the present studies was to investigate the effects of 5-HT(1B) receptor activation and antagonism on intracranial self-stimulation (ICSS) reward using a current-threshold ICSS task. Male Wistar rats were prepared with bipolar electrodes in the lateral hypothalamus. When stable baseline thresholds were established, the effects of the mixed 5-HT(1A)/1B receptor agonist, RU 24969 (0-1 mg/kg, SC), on ICSS behavior were assessed. Administration of this compound elevated ICSS thresholds without affecting response latencies, a measure of general motoric activity. The 5-HT(1B/1D) receptor antagonist, GR 127935 (0-10 mg/kg, SC), had no significant effect on ICSS behavior. However, pretreatment with an intermediate dose of GR 127935 (3 mg/kg), which was previously without effect on ICSS behavior, reversed the threshold-elevating effects of RU 24969 (1 mg/kg), suggesting the involvement of the 5-HT1B receptor in this effect of RU 24969 administration. Furthermore, pretreatment with RU 24969 (0.3 and 0.6 mg/kg), prior to 10 mg/kg cocaine hydrochloride, dose-dependently attenuated the threshold-reducing effects of cocaine. This result is interpreted as two opposing drug effects canceling each other out rather than a specific pharmacological antagonism. In conclusion, the results suggest that activation of 5-HT(1B) receptors reduces brain stimulation reward.

Animals↗
PubMed1999

Violent maternal deaths in North Carolina.

OBJECTIVE: To describe the frequency of domestic violence and substance abuse among a series of injury-related maternal deaths, determine awareness of the obstetric provider of domestic violence in those deaths by intimate partner homicide or depression in those deaths by suicide, and examine the relative risk of violent maternal death for unmarried status and non-white race. METHODS: A follow-up investigation was carried out for a case series of 41 injury-related maternal deaths identified from 1992 to 1994 in North Carolina. Death certificates, police records, newspapers, and records from medical examiners were used to ascertain mechanism and intent, history of alcohol or drug abuse, and, in cases of homicide, the relationship of the perpetrator to the victim. The obstetric provider was asked about his or her knowledge of domestic violence, depression, and drug or alcohol abuse relevant to the deceased victim. RESULTS: A total of 21 women (51.2%) were known to have or suspected of having been abused by either an intimate partner or an acquaintance. Of the 41 women, 11 (26.8%) were known to have abused drugs and/or alcohol. The obstetric provider was aware or suspicious of abuse in one third of homicides committed by an intimate partner. In three of the five suicide deaths, the obstetric provider was aware of depression. CONCLUSION: Domestic violence and drug and alcohol abuse were common in this series of injury-related maternal deaths. Domestic violence and depression were often unrecognized by the obstetric provider in these severe cases.

Adult↗
PubMed1999

Dopamine activation of endogenous cannabinoid signaling in dorsal striatum.

We measured endogenous cannabinoid release in dorsal striatum of freely moving rats by microdialysis and gas chromatography/mass spectrometry. Neural activity stimulated the release of anandamide, but not of other endogenous cannabinoids such as 2-arachidonylglycerol. Moreover, anandamide release was increased eightfold over baseline after local administration of the D2-like (D2, D3, D4) dopamine receptor agonist quinpirole, a response that was prevented by the D2-like receptor antagonist raclopride. Administration of the D1-like (D1, D5) receptor agonist SKF38393 had no such effect. These results suggest that functional interactions between endocannabinoid and dopaminergic systems may contribute to striatal signaling. In agreement with this hypothesis, pretreatment with the cannabinoid antagonist SR141716A enhanced the stimulation of motor behavior elicited by systemic administration of quinpirole. The endocannabinoid system therefore may act as an inhibitory feedback mechanism countering dopamine-induced facilitation of motor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice.

The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT1A receptor-mutant mice. These animals lack functional 5-HT1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.

Animals↗
PubMed1998

Serotonin1B receptor stimulation enhances cocaine reinforcement.

The effects of serotonin1B [5-hydroxytryptamine1B (5-HT1B)] receptor activation on cocaine reinforcement were investigated using intravenous cocaine self-administration by rats. The 5-HT1B receptor agonists 5-methoxy-3-1,2,3,6-tetrahydro-4-pyridinyl-1H-indole (RU 24969) (0.3-3 mg/kg), 3-(1,2,5, 6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94,253) (0.3-3 mg/kg), and 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3, 2-b]pyridine (CP 93,129) (3 and 10 micrograms, i.c.v.) each dose-dependently reduced the self-administration of a cocaine dose on the descending limb of the fixed-ratio 5 (FR-5) cocaine dose-effect function, in a manner similar to the effect produced by increasing the unit dose of cocaine. In addition, each of these 5-HT1B agonists lowered the threshold dose of cocaine that supported self-administration. These results are consistent with a 5-HT1B agonist-induced potentiation of cocaine reinforcement. On a progressive ratio schedule of reinforcement, RU 24969 and CP 94,253 dose-dependently (0.3-3 mg/kg) increased the highest completed ratio for cocaine self-administration, again by producing behavioral alterations similar to those induced by increasing the unit dose of cocaine. The effect of CP 94,253 was dose-dependently blocked by the 5-HT1B/1D receptor partial agonist 2'-methyl-4'-(5-methyl[1,2, 4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid[4-methodoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127, 935) (0.3-10 mg/kg) but was unaffected by the 5-HT1A receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl- benzamide (p-MPPI; 1-10 mg/kg). Self-administration behavior was not maintained when either RU 24969 or CP 94,253 was substituted for cocaine, indicating that these 5-HT1B agonists do not produce significant reinforcing effects alone. Together, these findings indicate that 5-HT1B receptor stimulation facilitates the reinforcing properties of cocaine. These results are in opposition to recent findings with 5-HT1B receptor knock-out mice and may have important ontogenic implications in the area of drug abuse research.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Simple microbore high-performance liquid chromatographic method for the determination of dopamine and cocaine from a single in vivo brain microdialysis sample.

A microbore chromatographic method for the analysis of both dopamine and cocaine from in vivo brain microdialysis samples is described. To eliminate the need for separate chromatographic systems for each analyte, post-column electrochemical and ultraviolet detection systems were arranged in series. The limit of quantitation for dopamine (5 fmol) was well within range for detecting dialysate concentrations of this neurotransmitter in rats which were in a baseline, drug-free state. The limit of quantitation for cocaine (0.5 pmol) was sufficient to detect brain cocaine levels following the peripheral administration of a low dose of this psychostimulant (5 mg/kg, i.p.). Estimates of dialysate dopamine and cocaine concentrations after 5, 10 and 20 mg/kg cocaine (i.p.) were in agreement with reports which utilized separate HPLC analyses for each analyte.

Animals↗
PubMed1998

The prevalence of domestic violence among women seeking abortion.

OBJECTIVE: To determine the prevalence of self-reported abuse in a population of women aged 18 years or older seeking elective pregnancy termination, and to compare abused and nonabused women with respect to the primary reasons for pregnancy termination. METHODS: A self-administered questionnaire was returned by 486 women seeking outpatient abortion. The survey included demographic information, abuse screening, and items regarding partner involvement/awareness of the pregnancy, and abuse as a determinant of the abortion decision. One open-ended item asking the primary reason for pregnancy termination was included. RESULTS: The prevalence of self-reported abuse in this population was 39.5%. White women were significantly more likely to report any history of abuse than nonwhite women. Relationship issues were the only reason for pregnancy termination given more often by women with an abuse history than by nonabused women. Women with abuse histories were significantly less likely than nonabused women to inform the partner of the pregnancy or to have partner support for or involvement in the abortion decision. CONCLUSION: The prevalence of abuse reported by women in this population suggests that many women seeking abortion services may have abuse histories. Abused women may have different reasons for pregnancy termination than nonabused women and may be more likely to make the abortion decision without partner involvement. When routine screening for abuse is included in abortion counseling, health providers have the opportunity for developing a safety plan and initiating appropriate referral.

Abortion Applicants↗
PubMed1998

Substance dependence as a compulsive behavior.

A compulsion to take a drug combined with a loss of control in limiting intake is the defining feature of substance dependence or addiction, and is the conceptual framework for the criteria of substance dependence or addiction outlined by the World Health Organization and the American Psychiatric Association. However, defining exactly what constitutes loss of control and compulsive drug taking at the level of animal models is a daunting task, and it is clear that no validated animal model exists for the whole syndrome of addiction. The present discussion redefines loss of control as a narrowing of the behavioral repertoire toward drug-seeking behavior and suggests that there are many sources of reinforcement that contribute to this behavioral focus on drug seeking. Evidence is presented demonstrating separate animal models for many of these sources of reinforcement as well as for most of the criteria for substance dependence. Evidence is also presented showing that the brain neurochemical systems involved in processing drug reward are altered by chronic drug exposure to contribute additional sources of reinforcement. Challenges for the future involve not only elucidation of the neurobiological substrates of the different behavioral components of addiction, but better animal models of these components with which to effect such studies.

Animals↗
PubMed1998

Neurocircuitry targets in ethanol reward and dependence.

Alcoholism is a complex behavioral disorder characterized by excessive consumption of ethanol, a narrowing of the behavioral repertoire toward excessive consumption, the development of tolerance and dependence, and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome. Recent work has begun to define the neurocircuits responsible for the two major sources of reinforcement key to animal models of excessive ethanol intake: positive and negative reinforcement. Ethanol appears to interact with ethanol-sensitive elements within neuronal membranes that convey the specificity of neurochemical action. Ethanol reinforcement appears to be mediated by an activation of GABA-A receptors, release of opioid peptides, release of dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic ethanol administration as reflected by opposite effects during acute ethanol withdrawal and by the recruitment of other neurotransmitter systems such as the stress neuropeptide corticotropin-releasing factor. Future challenges will include a focus on understanding how these neuroadaptive changes convey vulnerability to relapse in animals with a history of ethanol dependence.

Alcohol Drinking↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗