Prolonged nicotine exposure does not alter GABA(B) receptor-mediated regulation of brain reward function

Gamma-aminobutyric acid subtype B (GABA(B)) receptors play an important role in regulating brain reward function. Accumulating evidence suggests that chronic exposure to drugs of abuse may alter GABA(B) receptor function. The present studies investigated whether chronic nicotine administration, using a regimen that induces nicotine dependence, increased inhibitory regulation of brain reward function by GABA(B) receptors, as measured by intracranial self-stimulation (ICSS) thresholds in rats. Such an action of nicotine may contribute to the reward deficit observed during nicotine withdrawal. Nicotine-dependent and control rats received the GABA transaminase inhibitor gamma-vinyl-GABA or the GABA(B) receptor agonist CGP44532 according to a within-subjects Latin square design, and ICSS thresholds were assessed post-injection. Systemic administration of the lowest doses of GVG or CGP44532 did not alter reward thresholds in control or nicotine-treated rats, whereas the highest doses of each drug elevated thresholds similarly in both groups. Further, micro-infusion of CGP44532 directly into the ventral tegmental area elevated ICSS thresholds similarly in saline- and nicotine-treated rats. Overall, these data demonstrate that prolonged nicotine exposure did not alter GABA(B) receptor-mediated regulation of brain reward function, and suggest that alterations in GABA(B) receptor activity are unlikely to play a role in the brain reward deficits associated with spontaneous nicotine withdrawal.     

Current trends in infection imaging

Infection imaging is a field of intense interest in medicine because, despite the great advances in our understanding of microorganisms and the development of new antimicrobial agents, infection remains a major cause of patient morbidity and mortality. Nuclear Medicine for many years has an important role in this field. The significance of this role varies in different clinical situations, in some cases being complementary to other imaging modalities as in postoperative patients, and in some cases being the method of choice as in orthopaedic infections after implants have been placed. Today there are many agents in Nuclear Medicine capable in imaging infection. Each of them has its own advantages and drawbacks. In recent years there is an increased research in the field with new methods tested. Among them are labelled antibacterial agents, labelled antimicrobial peptides, monoclonal antibodies for leukocyte labelling, labelled liposomes, and (18)F-FDG-PET. In this short article there is an effort to briefly review these agents and their possible role in infection imaging.     

Costing nuclear medicine diagnostic procedures

To the Editor: Referring to a recent special report about the cost analysis of twenty-nine nuclear medicine procedures, I would like to clarify some basic aspects for determining costs of nuclear medicine procedure with various costing methodologies. Activity Based Costing (ABC) method, is a new approach in imaging services costing that can provide the most accurate cost data, but is difficult to perform in nuclear medicine diagnostic procedures. That is because ABC requires determining and analyzing all direct and indirect costs of each procedure, according all its activities. Traditional costing methods, like those for estimating incomes and expenses per procedure or fixed and variable costs per procedure, which are widely used in break-even point analysis and the method of ratio-of-costs-to-charges per procedure may be easily performed in nuclear medicine departments, to evaluate the variability and differences between costs and reimbursement - charges.     

Estrogens and brain function

Cognitive decline is well recognized during ageing but is often accelerated in women after menopause. Studies have shown that there are significant gender differences in brain ageing with significantly greater changes in brain structure, function and metabolism between females and males. Estrogens exert protective effects on neuronal cells in culture but the exact underlying mechanism for their neuroprotective effect in humans is not completely understood. Estrogens have been shown to affect the nervous system in many different ways: via binding to estrogen receptors (ERs) but also via multiple pathways. The results of small randomized trials and larger observational studies suggest a beneficial effect of estrogen therapy on cognitive function in symptomatic postmenopausal women. However, the results of the Women's Health Initiative Study (WHIMS) do not support this, at least not in women over the age of 65. Alzheimer's disease (AD) is two to three times more common in women than in men. Based on currently available data, routine therapeutic use of estrogens in women with AD is not justified but it may have a role in the prophylaxis of AD. The existing evidence supports the use of HRT only in women with menopausal symptoms for a few years following menopause.     

Respiratory failure: an overview

Respiratory failure is defined as a failure in gas exchange due to an impaired respiratory system--either pump or lung failure, or both. The hallmark of respiratory failure is impairment in arterial blood gases. This review describes the mechanisms leading to respiratory failure, the indices that can be used to better describe gas exchange abnormalities and the physiologic and clinical consequences of these abnormalities. The possible causes of respiratory failure are then briefly mentioned and a quick reference to the clinical evaluation of such patients is made. Finally treatment options are briefly outlined for both acute and chronic respiratory failure.     

Erectile dysfunction in men with obstructive sleep apnea syndrome: a randomized study of the efficacy of sildenafil and continuous positive airway pressure

The aim of this study was to compare the efficacy of sildenafil and continuous positive airway pressure (CPAP) in men with erectile dysfunction (ED) and obstructive sleep apnea syndrome (OSAS). In all, 30 men were randomly treated for 12 weeks either with sildenafil 100 mg before intercourse (15 men) or CPAP during night time sleep (15 men). Under sildenafil, 97/180 (53.9%) of attempted intercourses were successful compared to 33/138 (23.9%) under CPAP. The mean IIEF (erectile function domain score) was 12.9 and 9.3 after sildenafil and CPAP treatment, respectively (P=0.007), compared to 7.9 and 7 at baseline. In all, 53.3% of patients were satisfied with sildenafil and 20% with CPAP for ED treatment (P=0.058). Although sildenafil was superior to CPAP, comorbidities and OSAS per se possibly resulted in a lower effectiveness of sildenafil compared to that in the general population of ED men. While about half of the patients were not satisfied even with the more effective treatment, we conclude that a combination of the two therapeutic tools or a different therapeutic mode should be studied further.     

The ups and downs of addiction: role of metabotropic glutamate receptors

Drug addiction is characterized by drug-induced positive affect, followed by withdrawal-associated negative affect. Such drug-induced positive and negative affective states provide crucial sources of motivation that drive compulsive drug consumption. Metabotropic glutamate (mGlu) receptors, which are responsible for slow glutamate-mediated neurotransmission, are located throughout limbic and cortical brain regions that are implicated in drug addiction. Emerging evidence indicates that mGlu receptors regulate many behavioral actions of addictive drugs. In particular, group I mGlu receptors play an important role in regulating the reinforcing effects of drugs of abuse. Furthermore, group II mGlu receptors have been implicated in the synaptic adaptations that occur in response to chronic drug exposure and contribute to the aversive behavioral syndrome observed during withdrawal. These findings increase our understanding of the pathological processes that are associated with the development of drug addiction, and might ultimately lead to new therapies for the treatment of this disorder.     

The GABAB receptor agonists baclofen and CGP44532 decreased nicotine self-administration in the rat

Rationale Previous work has indicated a potential role for -aminobutyric acid-B (GABA_B) receptor agonists in treating drug addiction in humans. Specifically, GABA_B receptor agonists decreased cocaine, heroin and nicotine self-administration in rats.Objectives The purpose of the present studies was to extend previous findings by assessing the effects of additional GABA_B receptor agonists on nicotine self-administration and food-maintained responding, under both fixed and progressive ratio schedules in rats.Methods Male Wistar rats were exposed to a progressive ratio schedule where various nicotine doses were made available according to a within-subjects Latin Square design. Additional groups of rats were used to test the effects of the GABA_B receptor agonists baclofen and CGP44532 on nicotine self-administration (0.01 and 0.03 mg/kg per infusion) and food-reinforced responding on fixed and progressive ratio (CGP44532 only) schedules.Results Nicotine maintained stable self-administration under a progressive ratio schedule with a linear dose-response function (r=0.61). Both CGP44532 and (–)baclofen dose-dependently reduced nicotine self-administration on the fixed ratio schedule, and also decreased food-maintained responding at higher doses. Further, CGP44532 decreased breakpoints for nicotine and food at identical doses under the progressive ratio schedule.Conclusion The present data demonstrate that administration of GABA_B receptor agonists decreased intravenous nicotine self-administration under both fixed and progressive ratio schedules of reinforcement, possibly reflecting reduced rewarding effects of nicotine. Both baclofen and CGP44532 exhibited specificity for nicotine- versus food-maintained responding on the fixed ratio schedules but not on the progressive ratio schedule (CGP44532 tested only), indicating the potential usefulness of GABA_B receptor agonists as therapeutics for smoking cessation.     

Conditioned facilitation of brain reward function after repeated cocaine administration

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function.