Cue-induced cigarette craving and mixed emotions: A role for positive affect in the craving process

Craving is an important component of nicotine addiction, and extant research has demonstrated a clear link between cue-induced craving and negative affect, with mixed results in the positive affect domain. The current study was designed to test the idea that cue-reactive craving might be associated with a mixed emotional process, or the simultaneous experience of positive and negative affect. Participants were 86 non-deprived regular smokers and tobacco chippers who provided simultaneous ratings of positive and negative affect during cue exposure to pleasant, unpleasant, neutral and cigarette cues. Results indicated that self-reported craving was elevated in response to cigarette cues compared to other valenced cue types and craving was higher to pleasant cues than either neutral or unpleasant cues. Mixed emotional responses were higher to cigarette cues than other cue types. In addition, mixed emotional responses to cigarette cues predicted craving even after controlling for smoker type, difficulties regulating negative emotion, baseline craving level and mixed emotional responses to neutral cues. As the first study to investigate mixed emotions and cigarette craving, our results highlight the importance of examining the relationship between cue-reactive craving and emotional response using models of emotion that allow for measurement of nuanced emotional experience. In addition, our findings suggest that positive affect processes may indeed play a role in craving among non-deprived smokers.     

d-Amphetamine and punished responding: The role of catecholamines and anorexia

Rats were trained to press a lever for food on a schedule in which components of variable interval reinforcement (VI2) alternated with conflict components in which every response resulted in food delivery and footshock. Low doses of d-amphetamine selectively suppressed responding in the confliet component in a dose-dependent manner, whereas prefeeding suppressed responding in both components. Pretreatment with noradrenergic blocking agents (propranolol, phentolamine and phenoxybenzamine) did not diminish the suppressant effect of d-amphetamine, but this effect was reduced by pretreatment with alpha-methyl-para-tyrosine methylester and dopamine blockers (spiroperidol, haloperidol and clozapine) indicating that d-amphetamine was exerting its selective suppressant effect via the release of dopamine. It is suggested that the effects of low doses d-amphetamine on behaviour in conflict situations may provide a useful model for investigating the mode of action of neuroleptic drugs.     

The role of catecholamines in central antidiuretic and pressor mechanisms

Angiotensin II (AII), when delivered intraventricularly (IVT) produces an increase in blood pressure and release of antidiuretic hormone (ADH). In the experiments reported here we have investigated the role of central catecholamines in these responses. After central 6-hydroxydopamine (6-OHDA) treatment IVT, AII was less effective in producing a blood pressure increase or ADH release. Similar responses to IVT carbachol were also inhibited. Pressor responses to IVT phenylephrine were not significantly changed after 6-OHDA treatment although ADH release was decreased. In further analysis, both a dopamine blocker, haloperidol, and phentolamine, an α-adrenergic blocker inhibited the pressor response but not ADH release to IVT AII. Both effects may be explained by α-adrenergic blockade. Dopamine IVT alone was ineffective in producing either ADH release or a blood pressure increase and phenylephrine in high doses produced both effects. We conclude that noradrenergic mechanisms may be important as a common mediator of central sympathetic outflow. The ADH release produced by AII and carbachol may be by direct action of periventricular receptors which can be damaged non-specifically by 6-OHDA.     

The role of catecholamines in behavioral arousal during ontogenesis

Effect of catecholamine depletion on normal hyperactivity in the neonatal rat was examined. Both -methyl-para-tyrosine and reserpine significantly depressed behavioral arousal at 15 days postpartum, the age of greatest excitability. Heightened activity could be restored in drug-treated animals by administration of l-Dopa. These results indicate that the ontogenetic hyperactivity effect is a result of accelerated catecholamine function.This work was supported in part by National Institute of Mental Health Grants MH01562 and MH08501 to Byron A. Campbell.     

The role of catecholamines in formation and resolution of pulmonary oedema

Pulmonary oedema (PO) can emerge from mechanical disorders in pulmonary circulation leading to elevated fluid filtration in the lung, or from increased vascular permeability due to inflammatory or toxic injury of the alveolar-capillary barrier. A number of these disorders causing PO is associated with increased catecholamine (CA) levels in plasma and lung tissue and/or increased sympathetic activation such as neurogenic PO, high-altitude PO or PO in patients with phaeochromocytoma. Experimental CA stimulation in animals induced PO after less than one hour of infusion. Both alpha- and beta-adrenergic mechanisms are involved in the pathogenesis but also in the resolution of PO. CAs increase pulmonary capillary pressure and thus, enhance fluid filtration into the pulmonary interstitium. Additionally, by activation of proinflammatory cytokines, they induce pulmonary inflammation that may lead to capillary leak. Finally, they play an important role in the regulation of alveolar fluid clearance. The present paper considers the pathways by which CAs contribute to the development of PO of various origin.     

Neurokinin antagonists and their potential role in treating depression and other stress disorders

In the search for new therapeutic targets for depression and other stress-related disorders, much attention has focused on neurokinin-1 receptor (NK1r) antagonists. Progress toward NK2r and NK3r antagonists for the treatment of CNS disorders is also increasing, with multiple chemical series being reported. This review focuses on the patent literature since 2003, regarding these and related developments, for the medicinal chemistry of neurokinin antagonists as targets for depression and stress-related disorders.     

The face of the other: why we treat the human person differently

It is the dignity of the human person that provides the foundation of bioethics. But what is it about this notion of human dignity that demands we treat persons differently than we treat non-persons? Where does the concept of human dignity gain its “moral traction”? Closely following John Crosby—and with the help of Thomas Mann—we will see that it is in our incommunicability [what the Instruction Dignitas personae refers to as that which “each one carries in an indelible way” (Congregation for the Doctrine of the Faith, Instruction Dignitas Personae on Certain Bioethical Questions, n. 6, 1)] that we find the “is” that demands the “ought” of being treated differently.     

Nonadherence to antipsychotics: The role of positive attitudes towards positive symptoms

Approximately 50–75% of all patients do not take their antipsychotic medication as prescribed. The current study examined reasons why patients continue versus discontinue antipsychotic medication. We were particularly interested to which extent positive attitudes towards psychotic symptoms foster medication nonadherence. An anonymous online questionnaire was set up to decrease response biases. After a strict selection process, 91 participants with schizophrenia spectrum disorders were retained for the final analyses. On average, 6.2 different reasons for nonadherence were reported. Side-effects (71.4%), sudden subjective symptom improvement (52.4%) and forgetfulness (33.3%) emerged as the most frequent reasons for drug discontinuation. Approximately one fourth of all participants (27.3%) reported at least one positive aspect of psychosis as a reason for nonadherence. In contrast, patients reported on average 3.5 different reasons for adherence (e.g., want to live a normal life (74.6%) and fear of psychotic symptoms (49.3%)). The belief that paranoia represents a survival strategy (subscale derived from the Beliefs about Paranoia Scale) was significantly associated with nonadherence. Patients׳ attitudes toward medication and the individual illness model need to be carefully considered when prescribing medication. In particular for patients who are likely to discontinue psychopharmacological treatment complementary or alternative psychological treatment should be sought because of a largely increased risk of relapse in the case of sudden drug discontinuation.     

Meptazinol and pentazocine: plasma catecholamines and other effects in healthy volunteers.

1. This double-blind, random-order study was designed to compare the clinical effects and the plasma catecholamine responses after i.v. administration of meptazinol at doses 0.7 and 1.4 mg kg-1, pentazocine at doses 0.3 and 0.6 mg kg-1 and saline placebo to six healthy volunteers. 2. Mean arterial pressure was not affected by either drug. Heart rate showed slight drug-related changes. Respiratory rate fell slightly with both drugs, but independently of dose. 3. The critical flicker fusion threshold-test and Maddox wing readings could both clearly differentiate active drugs from placebo. Meptazinol caused more nausea and dysphoria as expressed with visual analogue scales. Both analgesics caused short-lived feelings of euphoria. 4. After pentazocine plasma noradrenaline increased almost two-fold in 10-20 min. The effect of meptazinol was slightly smaller, whereas meptazinol caused a pronounced increase in plasma adrenaline concentrations in two of six subjects. Pentazocine had a smaller, but significant effect on plasma adrenaline. 5. We conclude that the effects of meptazinol in healthy volunteers do not differ markedly from those of pentazocine, although it may cause more nausea and dysphoria. The pronounced increase in plasma adrenaline concentrations in two of six subjects calls for caution in its use in patients with cardiac diseases.     

中医辨证论治抑郁症的探讨

抑郁症是脑神与多脏腑之间的功能失调,精神抑郁为主要临床表现的疾病。西药在治疗抑郁症时,存在着疗程长、副作用大、治疗费用昂贵等问题。本文运用祖国医学基本理论,探讨抑郁症的辨证论治。中医治疗抑郁症中,以脏腑论治为中心,是辨证论治抑郁症的核心。     

Clozapine-induced myocarditis: role of catecholamines in a murine model

Clozapine, an atypical antipsychotic, is very effective in the treatment of resistant schizophrenia. However, cardiotoxicity of clozapine, particularly in young patients, has raised concerns about its safety. Increased catecholamines have been postulated to trigger an inflammatory response resulting in myocarditis, dilated cardiomyopathy, and death, although this has not yet been thoroughly studied. Here, we used the mouse to study whether clozapine administration could cause adverse myocarditis associated with an increase in catecholamines. Male Balb/C mice, age ~6 weeks, were administered 5, 10 or 25 mg/kg clozapine daily for 7 and 14 days; one group was administered 25 mg/kg clozapine plus 2 mg/kg propranolol for 14 days. Saline-treated mice served as controls. Heart sections were stained with hematoxylin and eosin for histopathological examination. Plasma catecholamines were measured with HPLC. Myocardial TNF-alpha concentrations were determined by ELISA. Histopathology of clozapine-treated mice showed a significant dose-related increase in myocardial inflammation that correlated with plasma catecholamine levels and release of TNF-alpha. Propranolol significantly attenuated these effects. A hypercatecholaminergic state induced by clozapine could explain the occurrence of myocarditis in some patients. Our data suggest that a beta-adrenergic blocking agent may be effective in reducing the incidence and severity of clozapine-induced myocarditis.     

The AGE of the matrix: chemistry, consequence and cure

Accumulation of advanced glycation endproducts (AGEs) plays a crucial part in the development of age-related diseases and diabetic complications. AGEs are formed in vivo via the so-called Maillard reaction: a reducing sugar reacts with a protein to form a labile Amadori product that is subsequently stabilized, producing an irreversible, non-enzymatic post-translational modification of the protein involved. Recently, it has become clear that, in addition to sugars, lipids play an important role in the initiation of AGE formation, and that genetic factors contribute to an individual's AGE levels. The highest AGE levels are found in tissues with slow turnover, such as tendon, skin, bone, amyloid plaques and cartilage. AGEs exert their effects by adversely affecting the mechanical properties of the matrix and by modulating tissue turnover. In cartilage, these detrimental effects result in tissue that is more prone to the development of osteoarthritis. As such, the accumulation of AGEs provides the first molecular mechanism explaining the age-related increase in the incidence of osteoarthritis. Ongoing research into anti-AGE-ing therapies, such as pyrodoxamine and thiazolium compounds, which are often developed to prevent AGE-induced diabetic complications, might also prove beneficial for the prevention of osteoarthritis.     

Clinical trials of antidepressants: the hidden face: where locus of control appears to play a key role in depression outcome

It remains difficult to determine in what measure improvements observed in clinical trials of antidepressants may be attributable to the psychological predispositions of the subjects. The present article focuses on the effect of a psychological variable, the Health Locus of Control, which measures the extent of a subject's belief that he is in control over his own health. The hypothesis is that depressed subjects whose locus of control is internal, i.e. who perceive themselves to be in control, rather than external, i.e. control perceived as being in others or just chance, will improve more markedly and consistently on the Hamilton Depression Rating Scale, across a number of clinical trials. Forty-nine depressive patients undergoing treatment with four different compounds were included, after a week's placebo run-in period, in a classical 42-day follow-up study comprising visits on days –7, 0, 10, 21; and 42. Interactions between the type of locus of control and the clinical course were investigated by MANOVA. Results show that with a classical design of clinical trials of antidepressants, locus of control plays a significant role if it is internal (P<0.001) in consolidating the improvement process, and that this is true irrespective of type of antidepressant. The relationship between the concept of locus of control and placebo effect is discussed.     

The significance of dopamine,versus other catecholamines,for L-DOPA induced facilitation of sexual behavior in the castrated male rat

The effects of a wide dose range of L-DOPA on male rat sexual behavior were investigated. The animals were castrated as adults and supplied with small amounts of testosterone propionate. It was found that doses of L-DOPA up to 2.5 mg/kg facilitated, while higher doses inhibited, sexual behavior in animals pretreated with pargyline, 20 mg/kg, + MK486, 50 mg/kg. The effects of L-DOPA on sexual behavior were not restricted to the copulatory act, but included elements preceding the copulatory act as well. Most of the facilitatory effects of L-DOPA 2.5 mg/kg were prevented by the dopamine receptor blocker pimozide, 0.10 mg/kg. It is concluded that dopamine is the catecholamine of major importance in mediating the L-DOPA induced facililation of sexual behavior in the castrated male rat. However, some elements of the copulatory act appear to be modified by nonadrenaline and/or adrenaline as well.     

The role of the PACAP signaling system in depression

Major Depressive Disorder (MDD) is a psychiatric condition that represents an important public health concern in modern society. Current pharmacological antidepressant treatments improve depressive symptoms through complex mechanisms that are incompletely understood. There is a consensus that in the clinic they act through the modulation of monoaminergic neurotransmission, primarily involving the serotonin and norepinephrine systems. Recent studies have suggested that action of antidepressants on synaptic plasticity is mediated by their regulatory influence not only upon small-molecule neurotransmitters, but also via neuropeptides which may act both as neurotransmitters and as neuromodulators. Prominent among these neuropeptides is PACAP, whose signaling system is intensively studied for its pleiotropic involvement in various physiological and pathological conditions. This review outlines the current knowledge concerning the PACAP signaling system's involvement in depressive disorders.     

The role of sigma receptors in depression

Behavioral models used to test potential antidepressants have shown that ligands that bind to sigma receptors possess "antidepressant-like" properties. The focus of this review is to discuss the literature concerning sigma receptors and their ligands, with respect to their antidepressants properties. In addition to the behavioral data, we discuss electrophysiological and biochemical models demonstrating sigma receptors' ability to modulate important factors in the pathophysiology of depression and/or the mechanisms of action of antidepressants such as the serotonergic neurotransmission in the dorsal raphe nucleus (DRN) and the glutamatergic transmission in the hippocampus. We also discuss the significance of these two systems in the mechanism of action of antidepressants. Sigma ligands have potential as antidepressant medications with a fast onset of action as they produce a rapid modulation of the serotonergic system in the DRN and the glutamatergic transmission in the hippocampus. As these effects of sigma ligands may produce antidepressant properties by completely novel mechanisms of action, they may provide an alternative to the antidepressants currently available and may prove to be beneficial for treatment-resistant depressed patients.