Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference, and delays morphine extinction in rats

Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor (NMDAR), play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 (GLT-1) (ceftriaxone) are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP) than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory (acquisition, extinction, and reinstatement of morphine preference) in rats. Results A low dose of neither MK-801 (0.05 mg/kg, i.p.) nor ceftriaxone (25 mg/kg, i.p.) alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist (MK-801) and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.     

Morphine acutely and persistently attenuates nonvesicular GABA release in rat nucleus accumbens

Withdrawal from repeated exposure to morphine causes a long-lasting increase in the reactivity of nucleus accumbens nerve terminals towards excitation. The resulting increase in action potential-induced exocytotic release of neurotransmitters, associated with behavioral sensitization, is thought to contribute to its addictive properties. We recently showed that activation of N-methyl-D-aspartate (NMDA) as well as dopamine (DA) D1 receptors in rat striatum causes tetrodotoxin-insensitive transporter-dependent GABA release. Since sustained changes in extracellular GABA levels may play a role in drug-induced neuronal hyperresponsiveness, we examined the acute and long-lasting effect of morphine on this nonvesicular GABA release in rat nucleus accumbens slices. The present study shows that morphine, through activation of mu-opioid receptors, reduces nonvesicular NMDA-induced [(3)H]GABA release in superfused nucleus accumbens slices. Moreover, prior repeated morphine treatment of rats (10 mg/kg, sc, 14 days) caused a reduction in NMDA-stimulated [(3)H]GABA release in vitro until at least 3 weeks after morphine withdrawal. This persistent neuroadaptive effect was not observed studying dopamine D1 receptor-mediated [(3)H]GABA release in nucleus accumbens slices. Moreover, this phenomenon appeared to be absent in slices of the caudate putamen. Interestingly, even a single exposure of rats to morphine (>2 mg/kg) caused a long-lasting inhibition of NMDA-induced release of GABA in nucleus accumbens slices. These data suggest that a reduction in nonvesicular GABA release within the nucleus accumbens, by enhancing the excitability of input and output neurons of this brain region, may contribute to the acute and persistently enhanced exocytotic release of neurotransmitters from nucleus accumbens neurons in morphine-exposed rats.     

Dopamine and serotonin release in dorsal striatum and nucleus accumbens is differentially modulated by morphine in DBA/2J and C57BL/6J mice

Numerous studies have demonstrated that genetic factors significantly influence opioid ability to induce behavioral modification in mice. This differential sensitivity has been extensively studied, particularly in the DBA/2J and C57BL/6J strains. In the present study, using the "in vivo" microdialysis technique in these strains, we investigated the effect of morphine administration on the extracellular levels of dopamine (DA), serotonin (5-HT), and their metabolites in the nucleus accumbens and dorsal striatum--areas thought to be involved in morphine-induced locomotor hyperactivity. In the nucleus accumbens, morphine (20 mg/kg) significantly increased extracellular levels of DA in both strains. However, in dorsal striatum the morphine-induced increase of extracellular DA was lower in DBA/2J mice than in C57BL/6J. Moreover, morphine significantly stimulated 5-HT and 5-hydroxyindolacetic acid (5-HIAA) release both in nucleus accumbens and dorsal striatum of C57BL/6J mice, whereas it decreased 5-HT release without modifying 5-HIAA levels in DBA/2J mice. These results suggest that the different behavioral and biochemical responses to acute morphine described in these two strains could be mediated by different sensitivity of both the dopaminergic and the serotonergic systems.     

Cervical catheter placement for intrathecal baclofen test dose: is it safe?

Introduction

Intrathecal baclofen testing is usually performed via a catheter inserted at the lumbar spine. However, in patients with scoliosis, the distorted anatomy and bone fusion from corrective spinal surgery obviates access at the lumbar spine.

Patients and methods

We report a method for inserting the intrathecal catheter via a posterior cervical approach and discuss our outcome. We describe our experience in 20 patients in whom intrathecal baclofen test catheter was inserted at the lower cervical spine. Data was collected prospectively.

Discussion

The procedure was successful in all 20 patients. There were no complications as a result of surgery or from baclofen test dose administration via a cervical catheter. Of the 20 patients, 15 went on to have baclofen pump implantation via a cervical catheter. In one patient, subsequent pump implantation procedure was unsuccessful due to presence of extradural scar tissue. In the remaining four patients pump implantation was declined due impending corrective spinal surgery or social reasons.

Conclusion

Our experience shows that low cervical catheter insertion for administration of a test dose of intrathecal baclofen and feasible and safe to perform via the method described.     

Differential behavioural sensitization to intermittent morphine treatment in alcohol-preferring AA and alcohol-avoiding ANA rats: role of mesolimbic dopamine

Alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Non-Alcohol) rats have well-documented differences in their voluntary ethanol consumption and brain opioidergic systems. The aim of the present study was to investigate whether these rat lines differ in their susceptibility to morphine-induced behavioural and neurochemical sensitization. The rats were given 15 injections of morphine (10 mg/kg, s.c.) or saline every other day. Locomotor activity and release of dopamine in the nucleus accumbens were monitored after a challenge with additional morphine injections (10 mg/kg) 1 and 5 weeks after withdrawal from the repeated treatment. Morphine increased locomotion more in the previously morphine-treated rats than in the saline-treated controls. Furthermore, AA rats were more sensitive to this effect of morphine than ANA rats. Accumbal morphine-induced dopamine release was significantly higher in the morphine-treated AA than ANA rats after the first challenge injection 1 week from withdrawal, but no differences were observed after the second challenge. The brain and plasma concentrations of morphine were similar among the lines suggesting that the differences in the effects of morphine cannot be explained in terms of differential pharmacokinetics of morphine in these lines. These data show that AA rats are more susceptible to morphine-induced behavioural sensitization than ANA rats. Furthermore, it suggests that mesolimbic dopamine has at best only a transient role in the expression of opioid-induced behavioural sensitization. The relationship between the mechanisms underlying the differential sensitivity of these rat lines to the effects of repeated morphine and voluntary ethanol drinking remains to be determined.     

Racial Differences in Mortality in Older Adults: Factors Beyond Socioeconomic Status

Background

Little is known about the simultaneous effect of socioeconomic status (SES), psychosocial, and health-related factors on race differences in mortality in older adults.

Purpose

This study examined the association between race and mortality and the role of SES, health insurance, psychosocial factors, behavioral factors, and health-related factors in explaining these differences.

Methods

Data consisted of 2,938 adults participating in the Health, Aging and Body Composition study. Mortality was assessed over 8?years.

Results

SES differences accounted for 60% of the racial differences in all-cause mortality; behavioral factors and self-rated health further reduced the disparity. The racial differences in coronary heart disease mortality were completely explained by SES. Health insurance and behavioral factors accounted for some, but not all, of the race differences in cancer mortality.

Conclusions

Race-related risk factors for mortality may differ by the underlying cause of mortality.     

1-Benzyl-1,2,3,4-tetrahydroisoquinoline,an Endogenous Neurotoxic Compound,Disturbs the Behavioral and Biochemical Effects of l-DOPA: In Vivo and Ex Vivo Studies in the Rat

Environmental factors and endogenously produced toxins, such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), are considered to be involved in the pathogenesis of Parkinson’s disease (PD). In this study, we investigated the impact of single and multiple 1BnTIQ (25 and 50 mg/kg i.p.) administration on l-DOPA-induced changes in the rate of dopamine and serotonin metabolism in the rat brain. Additionally, using in vivo microdialysis, we measured the impact of acute and multiple 1BnTIQ administrations on l-DOPA-induced dopamine release in the striatum. These data were compared with results from behavioral tests in which we measured the effect of 1BnTIQ and l-DOPA on locomotor activity. Finally, we determined the effect of the repeated administration of 1BnTIQ on the l-DOPA-induced elevation of caspase-3 activity in the hippocampus. An ex vivo neurochemical study indicated that both acute and chronic 1BnTIQ injections strongly inhibited l-DOPA-induced increases in the concentration of dopamine and all of its metabolites in dopaminergic structures. In contrast, in vivo microdialysis studies suggested that the differences in 1BnTIQ’s effects are dependent on the type of treatment. A single dose of 1BnTIQ intensified the elevation of dopamine release induced by l-DOPA administration (~1,300 %; P < 0.01), while multiple administrations of 1BnTIQ significantly enhanced the basal dopamine levels while partially diminishing the effects of l-DOPA injection (~200 %; P < 0.01). Additionally, we found that chronic administration of 1BnTIQ completely blocked the l-DOPA-induced increase in caspase-3 activity in the hippocampus. These findings indicate that both acute and chronic administrations of 1BnTIQ disturbs the behavioral and biochemical effects of l-DOPA in the rat. The data presented from ex vivo and in vivo studies clearly suggest that 1BnTIQ’s effects may be connected with the inhibition of DAT and/or COMT activity in the brain. Furthermore, elevated endogenous levels of 1BnTIQ may pose a serious risk in PD patients undergoing l-DOPA therapy.     

CCNP Heinz Lehmann Award Paper: Interference with AMPA receptor endocytosis: effects on behavioural and neurochemical correlates of amphetamine sensitization in male rats

Background

Behavioural sensitization has been linked to drug craving in both clinical and preclinical studies of addiction. Increased motor activity is accompanied by enhanced dopamine (DA) release, particularly in the nucleus accumbens (NAcc). The neural bases of sensitization are linked to alterations in synaptic connections that also underlie learning and memory. The present study uses an “interference” peptide, Tat-GluA2_3Y, that blocks long-term depression (LTD) at glutamatergic synapses by disrupting the endocytosis of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), to explore the role of this form of synaptic plasticity in the induction and maintenance of sensitization.

Methods

Rats were given 5 injections of d-amphetamine (d-AMPH, 1.0 mg/kg, intraperitoneal) every second day. Tat-GluA2_3Y, was administered by 2 different routes (intravenously and intracerebrally to the ventral tegmental area [VTA] or to the NAcc) before each injection of d-AMPH. After a 14-day drug-free period, expression of behavioural sensitization was evoked by a challenge injection of d-AMPH (0.5 mg/kg, intraperitoneal). Dopamine efflux in the NAcc was measured by high-pressure liquid chromatography with electrochemical detection analyses of brain dialysates on days 1, 9 and 24 of the intravenous peptide experiment.

Results

Systemic administration of Tat-GluA2_3Y during the induction phase blocked maintenance of behavioural sensitization and attenuated the maintenance of neurochemical sensitization. Intra-VTA infusion of Tat-GluA2_3Y before each administration of d-AMPH did not affect induction, but inhibited maintenance and subsequent expression of sensitization, whereas intra-NAcc infusion of the peptide did not affect induction or maintenance of sensitization.

Limitations

The relevance of behavioural sensitization in rodents is related to the development of craving and does not provide direct measures of drug reinforcement.

Conclusion

These findings confirm that drug-induced neuroplasticity is labile and may be subject to disruption at a time when long-lasting associations between drug reward and contextual stimuli are formed. Furthermore, the unique ability of Tat-GluA2_3Y to block maintenance of behavioural sensitization implicates LTD in the consolidation of essential associative memories. Tat-GluA2_3Y has the unique ability to disrupt functional neuroadaptations triggered by repeated psychostimulant exposure and therefore may protect against the development of craving and drug seeking behaviours.     

Predicting Condom Use Using the Information-Motivation-Behavioral Skills (IMB) Model: A Multivariate Latent Growth Curve Analysis

Background

The Information-Motivation-Behavioral Skills (IMB) model often guides sexual risk reduction programs even though no studies have examined covariation in the theory??s constructs in a dynamic fashion with longitudinal data.

Purpose

Using new developments in latent growth modeling, we explore how changes in information, motivation, and behavioral skills over 9?months relate to changes in condom use among STD clinic patients.

Methods

Participants (N?=?1281, 50% female, 66% African American) completed measures of IMB constructs at three time points. We used parallel process latent growth modeling to examine associations among intercepts and slopes of IMB constructs.

Results

Initial levels of motivation, behavioral skills, and condom use were all positively associated, with behavioral skills partially mediating associations between motivation and condom use. Changes over time in behavioral skills positively related to changes in condom use.

Conclusions

Results support the key role of behavioral skills in sexual risk reduction, suggesting these skills should be targeted in HIV prevention interventions.     

Multisystemic Therapy Compared to Telephone Support for Youth with Poorly Controlled Diabetes: Findings from a Randomized Controlled Trial

Background

Few interventions have effectively improved health outcomes among youth with diabetes in chronic poor metabolic control.

Purpose

This study aims to determine whether multisystemic therapy (MST), an intensive, home-based, tailored family treatment, was superior to weekly telephone support for improving regimen adherence and metabolic control among adolescents with chronic poor metabolic control.

Methods

A randomized controlled trial was conducted with 146 adolescents with types 1 or 2 diabetes. Data were collected at baseline, 7?months (treatment termination), and 12?months (6?months follow-up).

Results

Adolescents receiving MST had significantly improved metabolic control at 7 (1.01?% decrease) and 12?months (0.74?% decrease) compared to adolescents in telephone support. Parents of adolescents receiving MST reported significant improvements in adolescent adherence. However, adolescent-reported adherence was unchanged.

Conclusions

MST improved health outcomes among adolescents with chronic poor metabolic control when compared to telephone support. Home-based approaches may provide a viable means to improve access to behavioral interventions for such youth.     

Dose-dependent relapse of hiatus hernia after administration of intrathecal baclofen treatment—a rare complication

Introduction

Intrathecal baclofen treatment (ITB) is widely used in children with cerebral palsy. Although this treatment effectively reduces spasticity, diverse side effects are reported.

Case report

We report about a boy with severe asphyxia-induced encephalopathy with bilateral cerebral palsy. After starting the intrathecal baclofen treatment, he episodically showed symptoms of severe gastroesophageal reflux with pale skin color, vomiting, massive drooling, acid regurgitation, and reduced well-being. An open ventral semifundoplication was done some years ago to treat a gastroesophageal reflux. These symptomatic episodes occurred strongly dose-dependent and were not observed during the short test procedure.

Conclusion

For the first time, a strong dose-dependent treatment with ITB was documented as a cause for the above episodes and relapsing re-herniations.     

Confounding by Indication in Retrospective Studies of Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality

Introduction

Intracerebral hemorrhage (ICH) is a highly fatal disease with few proven treatments. Data to guide clinician decisions for therapies, including antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH have provided conflicting results. We investigated the effect of AED treatment on 90-day mortality after ICH in a large prospectively ascertained cohort.

Methods

We conducted a retrospective analysis of a prospectively assembled cohort of patients with ICH in the supratentorial regions, comparing 90-day mortality and modified Rankin Score among 543 patients treated with AED during hospitalization and 639 AED-free ICH. Supratentorial ICH location was categorized as lobar or deep hemispheric.

Results

Multivariate analysis demonstrated an association between AED treatment and reduced 90-day mortality in supratentorial ICH (OR?=?0.62, 95?% CI 0.42?C0.90, p?=?0.01) and the subset of lobar ICH (OR?=?0.49, 95?% CI 0.25?C0.96, p?=?0.04). When analyses were restricted to subjects surviving longer than 5?days from ICH, however, no association between AED treatment and a 90-day outcome, regardless of hemorrhage location (all p?>?0.15), was detected, despite more than adequate power to detect the originally observed association.

Conclusion

These results suggest that AED treatment in acute ICH is not associated with 90-day mortality or outcome and that any detected association could arise by confounding by indication, in which the most severely affected patients are those in whom AEDs are prescribed. They provide a cautionary example of the limitations of drawing conclusions about treatment effects from observational data.     

The potential anti-addictive agent, 18-methoxycoronaridine, blocks the sensitized locomotor and dopamine responses produced by repeated morphine treatment

18-Methoxycoronaridine (18-MC), a novel synthetic iboga congener, attenuates the reinforcing efficacy of morphine, disrupts some signs of morphine withdrawal in physically dependent rats and attenuates the dopamine response in the nucleus accumbens to acute morphine. The present study further investigated the interactions between 18-MC and morphine by examining the effects of 18-MC (40 mg/kg, i.p., 19 h earlier) on the expression of dopamine sensitization in the nucleus accumbens in response to morphine (20 mg/kg, i.p.) and on the dose-effect curves for morphine-induced locomotion (0-30 mg/kg, i.p.) in rats treated either acutely or repeatedly (five, once daily, injections of 20 mg/kg, i.p.) with morphine. Compared to vehicle pretreated controls, 18-MC increased the potency of morphine, shifting the dose-response curve to the left, in acute morphine treated rats; however, 18-MC did not alter the potency of morphine in rats treated repeatedly with morphine. Repeated morphine administration induced locomotor sensitization in approximately 50% of the rats tested; in vehicle pretreated rats, the morphine dose-response curve was shifted to the left in sensitized as compared to non-sensitized rats. In 18-MC pretreated rats, sensitized and non-sensitized rats responded similarly to morphine, revealing a blockade of sensitization by 18-MC. Consistent with this behavioural finding, 18-MC pretreatment completely abolished the sensitized dopamine response in the nucleus accumbens expressed by rats repeatedly treated with morphine. It is suggested that the potential anti-addictive efficacy of 18-MC might be related to an ability to restore normal functioning to a hypersensitive mesolimbic dopamine system produced by previous repeated morphine administration.     

Nicotine-induced behavioral sensitization is associated with extracellular dopamine release and expression of c-Fos in the striatum and nucleus accumbens of the rat

It is well known that repeated injections of nicotine produce progressively larger increases in locomotor activity, an effect referred to as behavioral sensitization. This study was carried out to investigate the neural mechanisms underlying nicotine-induced behavioral sensitization using in vivo microdialysis and Fos-like immunohistochemistry (FLI). Rats were given repeated injections of saline or nicotine (0.4 mg/kg s.c., twice daily for 7 days) followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine produced a much larger increase in locomotor activity in nicotine-pretreated rats (659.1+/-94.9 counts/2 h) than in saline-pretreated rats (218.1+/-61 counts/2 h). A direct local challenge of nicotine (1 or 5 mM) via a microdialysis probe in the nucleus accumbens or striatum induced a much greater dose-dependent increase of dopamine (DA) output in nicotine-pretreated rats than in saline-pretreated rats. Furthermore, in parallel with the behavioral and biochemical data, systemic challenge with nicotine produced marked Fos-like immunohistochemistry in the nucleus accumbens and the striatum in the nicotine-pretreated rats. Taken together, this study demonstrates that behavioral sensitization is clearly associated with an increase in DA release and activation of Fos-like immunoreactive cells in the striatum and the nucleus accumbens produced by repeated nicotine treatment. Our results strongly suggest that the striatum and the nucleus accumbens may play a major role in nicotine-induced behavioral sensitization. The present results are discussed in terms of the development and expression of nicotine-induced behavioral sensitization.     

Filicide in Austria and Finland - A register-based study on all filicide cases in Austria and Finland 1995-2005

Background

It has been suggested that dopamine dysfunction may play a role in bipolar disorder (BD). An indirect approach to examine this issue was developed, focusing on associations between dopamine proxy measures observed in BD (dopamine-related clinical traits using tardive movement syndromes as dopamine proxy measure of reference).

Methods

3459 eligible bipolar patients were enrolled in an observational study. Incidence rates of tardive movement syndromes (tardive dyskinesia and tardive dystonia; TDD) were examined. A priori hypothesized associations between incident TDD and other dopamine proxies (e.g. prolactin-related adverse effects, bipolar symptoms) were tested over a 2 year follow-up period.

Results

The incidence rate of tardive syndromes was 4.1 %. Incident TDD was independently associated not only with use of antipsychotics, but also with more severe bipolar symptoms, other extrapyramidal symptoms and prolactin-related adverse effects of medication.

Conclusion

Apart from the well-known association with antipsychotics, development of TDD was associated with various other dopamine proxy measures, indirectly supporting the notion of generalised dopamine dysregulation in BD.     

Challenges in diagnosing SSPE

Purpose

The typical clinical presentation of subacute sclerosing panencephalitis (SSPE) includes behavioral and intellectual changes followed by myoclonia. However, there are a considerable number of SSPE cases which present with distinct clinical features that can lead to a diagnostic difficulty. In this report, we summarize the clinical features of patients with SSPE who have uncommon presentations or features of the disease or coexisting medical conditions which may lead to diagnostic difficulties.

Methods

We studied 173 patients, all under the age of 17. Patients were included in the study group according to following criteria: onset of the disease before age 2?years, seizures occurring before the onset of myoclonia and/or behavioral symptoms, extrapyramidal or cerebellar signs and ocular manifestations as initial presenting symptoms, fulminant course including coma or death within 6?months. Additionally, patients with onset of SSPE at the setting of a known neurological disorder are defined as another group in the study.

Results

Out of 173 patients with SSPE who were followed in two neurology centers, 31 (17.9%) met our criteria.

Conclusions

We found a relative high frequency of these clinical features. Our findings suggest that clinicians should be aware of this clinical characteristics and rule out the disease in cases were other common causes have been excluded, especially in countries with insufficient measles immunization     

Effects of Clozapine,Haloperidol, and Fluoxetine on the Reversal of Cocaine-Induced Locomotor Sensitization

Objective

Repeated treatment with psychostimulants induces sensitization of the dopaminergic system in the brain. Dopaminergic sensitization has been proposed as a mechanism of psychosis. Although antipsychotics block the expression of sensitized behavior, they are ineffective for reversing the sensitized state. We investigated the effect of clozapine, haloperidol, and fluoxetine on the reversal of cocaine-induced behavioral sensitization.

Methods

Male ICR mice were sensitized to cocaine with repeated treatment. Animals were then split into four groups, and each group was treated with vehicle or one of the above drugs for 5 days. After a 3-day drug washout, locomotor activity was assessed before and after a cocaine challenge.

Results

Clozapine reversed the sensitized state, whereas haloperidol did not. Fluoxetine seemed to reverse the sensitization partially.

Conclusion

We confirmed that D₂ blockade was not effective for reversing sensitization. The reversal by clozapine is partially explained in terms of its strong 5-HT₂ and weak D₂ affinity. The partial reversal by fluoxetine seemed to be related to its serotonin-augmenting action.     

A Psychoeducational Intervention (SWEEP) for Depressed Women with Diabetes

Background

Clinically significant depression is present in 25?% of individuals with type 2 diabetes, its risk being doubled in women.

Purpose

To examine the effectiveness of the Study of Women??s Emotions and Evaluation of a Psychoeducational (SWEEP), a group therapy for depression treatment based on cognitive behavioral therapy principles that was developed for women with type 2 diabetes was conducted.

Methods

Women with significantly elevated depression symptoms (Center for Epidemiologic Studies Depression Scale ??16) were randomized to SWEEP (n?=?38) or usual care (UC, n?=?36).

Results

Multilevel modeling indicated that SWEEP was more effective than UC in reducing depression (mean difference of ?15 vs. ?7, p?<?.01), decreasing trait anxiety (mean difference of ?15 vs. ?5, p?<?.01), and improving anger expression (mean difference of ?12 vs. ?5, p?<?.05). Although SWEEP and UC had improvements in fasting glucose (mean difference of ?24 vs. ?1?mg/dl) and HbA1c (mean difference of ?0.4 vs. ?0.1?%), there were no statistically significant differences between groups.

Conclusions

SWEEP was more effective than UC for treating depressed women with type 2 diabetes. Addition of group therapy for depression meaningfully expands the armamentarium of evidence-based treatment options for women with diabetes.     

Inhibition of nitric oxide synthase does not block the development of sensitization to the behavioral activating effects of amphetamine

Pretreatment with the nitric oxide (NO) synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), a competitive blocker of NO production, did not interfere with the development of sensitization to the behavioral activating effects of amphetamine (AMPH). On five pre-exposure sessions, at 3-day intervals, rats were given two i.p. injections, either 50 mg/kgL-NAME 30 min prior to 1.5 mg/kgD-AMPH sulfate, saline and AMPH,L-NAME and saline, or saline only.L-NAME reduced the levels of activity recorded during the pre-exposure session but had no effect on the degree of sensitization shown to a challenge injection of 0.5 mg/kg AMPH given 10 days later. A separate study using in vivo microdialysis showed that pretreatment withL-NAME did not alter AMPH-stimulated dopamine release in nucleus accumbens.     

Ultrasound-guided refilling of an intrathecal baclofen pump—a case report

Introduction

Refilling intrathecal baclofen (ITB) pumps can be difficult because many patients gain excessive weight after implantation due to their reduced expenditure of energy on muscle spasticity.

Methods

We report a case of a 12-year-old girl with spastic quadriplegia who gained 20 lbs after pump implantation. It was necessary to identify the access port of her pump by ultrasonography during drug refilling so as to avoid multiple needle punctures.

Results

The access port of the pump was readily visible by ultrasonography and stood out from other parts of the pump.

Conclusion

Localisation of the access ports of ITB pumps by ultrasonography proved to be a feasible and easy technique for refilling the drug reservoir in patients with excessive weight gain and abundant subcutaneous fat after ITB therapy.