Relationship between Craving and Early Relapse in Alcohol Dependence: A Short-Term Follow-up Study

Patients need to be advised about the risks and to reduce the dose, in case of excessive drowsiness. In in-patient settings where intense monitoring is not possible due to lack of trained staff, a fixed dose regimen is preferred. The findings of this double‐blind RCT demonstrate for the first time that four sessions of ApBM significantly delays the time to first drink among ApBM participants during the initial months post‐discharge, extending median time to first lapse until day 53 (relative to day 12 in controls).

The CRF produced in those areas is thought to play a role in the behavioral stress response (as opposed to the endocrine stress response characterized by the release of stress hormones from the adrenal glands that results from the actions of hypothalamic CRF and pituitary ACTH). The action of CRF is mediated through G-protein–coupled CRF1 receptors in the pituitary and through CRF1 and CRF2 receptors in brain areas such as the extended amygdala (Dautzenberg and Hauger 2002). Other evidence for a role of GABA systems in alcohol consumption comes from studies of mice lacking different variants of PKC. Mice that lacked one type of PKC, and in which GABAA receptor function was less sensitive to potentiation by ethanol, demonstrated increased ethanol self-administration compared with normal mice (Harris et al. 1995).

• Awareness and clarity of emotion could represent early processing components of emotional competence.26 Indeed, only by acknowledging and identifying which emotions one is experiencing can one regulate negative affective states.
• Roberts, Griffin, and Lopez provide an overview of these dependence and drinking models where escalation of alcohol intake has been demonstrated in rats and mice under limited- or continuous-access conditions when alcohol is provided in the home cage or in an operant conditioning paradigm.
• Date of first lapse was recorded for non‐abstinent participants to determine time to first lapse.
• Because the influx of cations through iGluRs during excitatory neurotransmission is critical for inducing plasticity, it is not surprising that acute ethanol exposure negatively affects the induction of NMDA-dependent long-term potentiation as well as promotes long-term depression (Blitzer et al. 1990; Hendricson et al. 2002).

TREATMENT OF ACUTE ALCOHOL WITHDRAWAL SYNDROME

Participants with current mood or anxiety disorders reported smoking a greater number of cigarettes than participants without a current mood or anxiety disorder. Participants who reported having any of the four current disorders were more likely to report the presence of another current disorder. The Brief Symptom Inventory (BSI; Derogatis and Melisaratos, 1983), a 53-item brief version of the Symptom Checklist-90—revised (Derogatis and Unger, 2010), was administered at baseline, the end of treatment, and at three, six, nine, and twelve-month follow-up appointments. It is a psychometrically sound measure of psychological functioning, and the Global Severity Index (BSI-Global Severity) acts as a measure of overall psychological distress reflective of symptoms of psychopathology (Derogatis and Unger, 2010).

An Animal Model of Alcohol Dependence to Screen Medications for Treating Alcoholism

Conversely, mice that lacked another type of PKC, and in which GABAA receptor function was more sensitive to potentiation by ethanol, consumed less ethanol (Song and Messing 2005). These animals appear to be more sensitive to ethanol’s aversive effects and less sensitive to its rewarding effects (Newton and Messing 2007). Together these findings suggest that potentiation of GABA transmission by ethanol modulates the animals’ motivation to consume ethanol. There are numerous subtypes of serotonin receptors (Hoyer et al. 2002), and it is possible that serotonin can affect alcohol drinking by activating specific receptors. For example, activation of 5-HT2C or 5-HT1A serotonin receptors reduces alcohol consumption (Long et al. 1996; Tomkins et al. 2002).

Reduced drinking: pro and con

The current study examined tobacco withdrawal symptoms and withdrawal-related discomfort and relapse in smokers with and without current mood disorders, anxiety disorders, alcohol use disorders (AUD), and substance use disorders (SUD). Extrapolation from the alcohol and drug use motivation literature, as well as models of relapse prevention, suggests that the “removal” of alcohol use may have several psychological consequences. The notion that individuals use alcohol for both the euphoric and positive reinforcement effects (e.g. Cooper et al., 1995, Goldman et al., 1999), as well as for reasons of “self-medication” or negative reinforcement properties (e.g. Greeley and Oei, 1999, Sayette, 1999, Sher, 1987) enjoys a long history of support. As such, cessation of alcohol use (a goal of many treatments) may inadvertently result in concurrent increases in subjective distress due to the removal of a potential “coping strategy” and/or pleasurable activity.

High comorbidity with other mental illnesses, including:

On the postsynaptic cell, the released neurotransmitter binds to its receptors, thereby triggering changes in the postsynaptic cell that either promote or inhibit the formation of new action potentials. Neurotransmitters whose binding to their receptors promotes the formation of a new action potential are called excitatory neurotransmitters; conversely, neurotransmitters whose binding to their receptors makes generation of a new action potential more difficult are called inhibitory neurotransmitters. The axon tip of a signal-emitting, or presynaptic, neuron and the synaptic region of the signal-receiving, or postsynaptic, neuron are separated by a small gap (i.e., synaptic cleft). To allow the signal to cross this gap, the presynaptic neuron releases a neurotransmitter that can migrate across the synaptic cleft and interact with docking molecules (i.e., receptors) on the postsynaptic neuron. The neurotransmitter release is initiated by the arrival of an action potential at the axon tip.

• Alcoholism is a chronic relapsing disease, and relapse represents a major challenge to treatment efforts.
• Subsequently, Amanda Roberts reviewed evidence that increased drinking induced by stress was dependent on corticotropin-releasing factor (CRF).
• One key element of relapse is craving—that is, the desire to repeat the effect(s) of a previously experienced psychoactive substance (Spanagel and Holter 1999; Spanagel and Kiefer 2008).
• The development of preclinical models has played a central role in expanding our knowledge of the myriad biological, genetic, and environmental forces that influence excessive alcohol consumption.

Craving

In particular, we found difficulty in the awareness and understanding of emotion, precisely to identify correctly the emotions. The “Emotional Clarity” seems to be the emotional difficulty that characterized also the group with a high level of craving at discharge and the individuals with early relapse, suggesting the importance of this function as a preliminary factor in emotion regulation. They underwent a brief semi-structured interview at admission and completed a battery of five self-report questionnaires between days 7 and 10 of alcohol abstinence (T0) and 3 days prior to discharge (T1). Initial screening interviews were scheduled for all potential participants who were referred to the treatment site or responded to newspaper advertisements. Eligible participants were scheduled for a baseline assessment and randomized to therapists who either received or did not receive therapeutic alliance feedback throughout treatment.

A small study showed that buspirone, a 5-HT 1A agonist, also had prophylactic effects in P rats. These findings show that alcohol-preferring P rats exhibit anxiety-like behavior more readily following exposure to ethanol-containing diets and that this behavior is counteracted more readily by pretreatment with a CRF 1 receptor antagonist than with BZD or 5-HT 2C receptor antagonists. Animal models designed to examine different facets of alcohol-related behaviors have been developed to study genetic and neurobiological factors underlying alcoholism and alcohol abuse.

If it gives the same response when it receives another compound, such as an iGluR antagonist, this indicates that the antagonist produces an effect that “feels” like alcohol to the animal. The affected brain regions include the prefrontal cortex and a group of structures known as the extended amygdala, including the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST). Although there is no specific alcohol receptor, certain “receptive elements” (e.g., receptor proteins) have been described that are affected by low concentrations of ethanol (Tabakoff and Hoffman 1983). In addition to subunit composition and association with other proteins, posttranslational modification also influences the exact function of specific GABAA receptor molecules. At that point, other enzymes perform modifications, such as addition of phosphate groups (i.e., phosphorylation), that can influence receptor function (Brandon et al. 2002; Sigel 1995) and trafficking (Kittler and Moss 2003).

High concentrations of ethanol inhibited the normal responses to mGluR5 activation in cells into which the receptors had been artificially introduced (i.e., in a heterologous cell system) (Minami et al. 1998). The opioid peptides—endorphins (teal), enkephalins (purple), and dynorphins (blue)—and the neurotransmitter dopamine are involved in the processes of reward and reinforcement. Endorphin-producing neurons are located primarily in the arcuate nucleus alcohol dependence, withdrawal, and relapse pmc (ArcN) of the hypothalamus and the nucleus tractus solitarius (NTS); they extend to and release endorphin in various brain areas (purple).