Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

A case of mistaken identity: HSPs are no DAMPs but DAMPERs

Until recently, the immune system was seen solely as a defense system with its primary task being the elimination of unwanted microbial invaders. Currently, however, the functional significance of the immune system has obtained a much wider perspective, to include among others the maintenance and restoration of homeostasis following tissue damage. In this latter aspect, there is a growing interest in the identification of molecules involved, such as the so-called danger or damage-associated molecular patterns (DAMPs), also called alarmins. Since heat shock proteins are archetypical molecules produced under stressful conditions, such as tissue damage or inflammation, they are frequently mentioned as prime examples of DAMPs (Bianchi, J Leukoc Biol 81:1–5, 2007; Kono and Rock, Nat Rev Immunol 8:279–289, 2008; Martin-Murphy et al., Toxicol Lett 192:387–394, 2010). See for instance also a recent review (Chen and Nunez, Science 298:1395–1401, 2010). Contrary to this description, we recently presented some of the arguments against a role of heat shock protein as DAMPs (Broere et al., Nat Rev Immunol 11:565-c1, 2011). With this perspective and reflection article, we hope to elaborate on this debate and provide additional thoughts to further ignite this discussion on this critical and evolving issue

Immune response to gut escherichia coli and susceptibility to adjuvant arthritis in the rats

We have investigated the humoral immune response to antigens of predominant gut aerobic bacterial strains (i.e. Escherichia coli) over the course of adjuvant arthritis and oil-induced arthritis in two inbred rat strains: Dark Agouti (DA) and Albino Oxford (AO). We report the presence of antibodies specific to proteins of Escherichia coli in molecular weight range between 20-30 kDa in sera of diseased DA rats, and the absence of these antibodies in the sera of AO rats. In DA rats, CFA and IFA provoked a stronger antibody response to Escherichia coli, especially of the IgG2b antibody class. Intramuscular administration of Escherichia coli preceding the adjuvant arthritis induction had no effect on the development and course of disease, as well as on the activation of T cells in the draining inguinal lymph nodes. Higher serum levels of natural and induced IgA antibodies, combined with a higher CD3(+)CD26(+) cell percentage were found in AO rats. The observed correlation between the serologic response to commensal flora and rats' genetic background as a defining factor for arthritis susceptibility may contribute to the process of creating a favorable (or less favorable) milieu for arthritis development

Altering the Motivational Function of Nicotine through Conditioning Processes

The collection of chapters in this 55th Nebraska Symposium on Motivation Volume clearly highlights that effective strategies for reducing compulsive tobacco use will require a multifaceted approach in which genetic, neurobiological, individual, and cultural factors are considered. It is difficult, if not impossible, to predict where the next important breakthrough will come from (Bevins & Bardo, 2004; Dethier, 1966; Laidler, 1998). Accordingly, further research that extends and challenges current theory and practice at each of these levels of analysis is needed. The continuing focus of our research program, and the topic of the present chapter, is on the role of Pavlovian conditioning processes involving nicotine. Theoretical and empirical approaches to nicotine dependence that include Pavlovian conditioning processes have lead to important advances in our understanding and treatment of chronic tobacco use (e.g., see Rose, Chapter 8 and Tiffany, Warthen, & Goedecker, Chapter 10 in current Volume). These approaches conceptualize the drug as an unconditioned stimulus (US) or reinforcer. That is, the pharmacological effects of the drug (e.g., reward, analgesia, psychomotor stimulation) enter into an association with stimuli that reliably co-occur with these effects (e.g., paraphernalia, situational cues). Later exposure to these conditioned stimuli (CSs) can evoke conditioned responses (CRs) that increase the chances an individual will seek drug. More recently, we have suggested that the interoceptive stimulus effects of nicotine might also serve as a CS for other appetitive non-drug outcomes (i.e., USs) and/or a stimulus that occasions whether other CS-US associations will or will not occur (i.e., an occasion setter or facilitator; see Bevins & Palmatier, 2004). We have further suggested that such an associative learning history could impact the tenacity of nicotine addiction—e.g., shorten the time between experimentation and dependence, increase the difficulty of quitting, make sustaining abstinence more difficult, etc. At the current time these suggestions are speculative. With this in mind, the present chapter will review the research in this area, as well as highlight some of its historical precursors and suggest some possible future directions for research. In doing so, hopefully the reader will gain an appreciation for how this approach might lead to further insight into how Pavlovian conditioning processes can alter the motivational function of nicotine in a manner that contributes to chronic tobacco use

Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats

Abstract: Rationale $\gamma$-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA$_B$ receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA$_B$ receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA$_B$ receptor agonists, GABA$_B$ receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists. Objectives and methods: We examined whether the acute effects of the GABA$_B$ receptor positive modulator N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) on nicotine self- administration and food-maintained responding under a fixed-ratio 5 schedule of reinforcement were maintained after repeated administration. The effects of acute BHF177 administration on cue-induced nicotine- and food-seeking behavior, a putative animal model of relapse, were also examined. Results: Repeated administration of BHF177 for 14 days decreased nicotine self-administration, with small tolerance observed during the last 7 days of treatment, whereas BHF177 minimally affected food-maintained responding. Acute BHF177 administration dose-dependently blocked cue-induced reinstatement of nicotine-, but not food-, seeking behavior after a 10-day extinction period. Conclusions: These results showed that BHF177 selectively blocked nicotine self-administration and prevented cueinduced reinstatement of nicotine seeking, with minimal effects on responding for food and no effect on cue-induced reinstatement of food seeking. Thus, GABA$_B$ receptor positive modulators could be useful therapeutics for the treatment of different aspects of nicotine dependence by facilitating smoking cessation by decreasing nicotine intake and preventing relapse to smoking in humans

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Nicotinic receptors

Regulation of normal or abnormal behaviour is critically controlled by the central serotonergic systems. Recent evidence has suggested that serotonin (5-HT) neurotransmission dysfunction contributes to a variety of pathological conditions, including depression, anxiety, schizophrenia and Parkinson’s disorders. There is also a great amount of evidence indicating that 5-HT signalling may affect the reinforcing properties of drugs of abuse by the interaction and modulation of dopamine (DA) function. This chapter is focused on one of the more addictive drugs, nicotine. It is widely recognised that the effects of nicotine are strongly associated with the stimulatory action it exhibits on mesolimbic DAergic function. We outline the role of 5-HT and its plethora of receptors, focusing on 5-HT2 subtypes with relation to their involvement in the neurobiology of nicotine addiction. We also explore the novel pharmacological approaches using 5-HT agents for the treatment of nicotine dependence. Compelling evidence shows that 5-HT2C receptor agonists may be possible therapeutic targets for smoking cessation, although further investigation is required.peer-reviewe