Recent brain-imaging studies revealed that the development and maintenance of alcohol dependence is determined by a complex interaction of different neurotransmitter systems and multiple ...psychological factors. In this context, the dopaminergic reinforcement system appears to be of fundamental importance. We focus on the excitatory and depressant effects of acute versus chronic alcohol intake and its impact on dopaminergic neurotransmission. Furthermore, we describe alterations in dopaminergic neurotransmission as associated with symptoms of alcohol dependence. We specifically focus on neuroadaptations to chronic alcohol consumption and their effect on central processing of alcohol-associated and reward-related stimuli. Dysfunctional reward processing, impaired reinforcement learning and increased salience attribution to alcohol-associated stimuli enable alcohol cues to drive alcohol seeking and consumption. Finally, we will discuss how the neurobiological and neurochemical mechanisms of alcohol-associated alterations in reward processing and learning can interact with personality traits, cognition and emotion processing.
This study aims to describe and analyze healthy individuals’ expressed experiences of touch massage (TM). Fifteen healthy participants received whole body touch massage during 60 minutes for two ...separate occasions. Interviews were analyzed by narrative analysis. Four identifiable storyline was found, Touch massage as an essential need, in this storyline the participants talked about a desire and need for human touch and TM. Another storyline was about, Touch massage as a pleasurable experience and the participants talked about the pleasure of having had TM. In the third storyline Touch massage as a dynamic experience, the informants talked about things that could modulate the experience of receiving TM. In the last storyline, Touch massage influences self-awareness, the participants described how TM affected some of their psychological and physical experiences. Experiences of touch massage was in general described as pleasant sensations and the different storylines could be seen in the light of rewarding experiences.
The allostatic theory of drug abuse describes the brain's reward system alterations as substance misuse progresses. Neural adaptations arising from the reward system itself and from the antireward ...system provide the subject with functional stability, while affecting the person's mood. We propose a computational hypothesis describing how a virtual subject's drug consumption, cognitive substrate, and mood interface with reward and antireward systems. Reward system adaptations are assumed interrelated with the ongoing neural activity defining behavior toward drug intake, including activity in the nucleus accumbens, ventral tegmental area, and prefrontal cortex (PFC). Antireward system adaptations are assumed to mutually connect with higher-order cognitive processes occurring within PFC, orbitofrontal cortex, and anterior cingulate cortex. The subject's mood estimation is a provisional function of reward components. The presented knowledge repository model incorporates pharmacokinetic, pharmacodynamic, neuropsychological, cognitive, and behavioral components. Patterns of tobacco smoking exemplify the framework's predictive properties: escalation of cigarette consumption, conventional treatments similar to nicotine patches, and alternative medical practices comparable to meditation. The primary outcomes include an estimate of the virtual subject's mood and the daily account of drug intakes. The main limitation of this study resides in the 21 time-dependent processes which partially describe the complex phenomena of drug addiction and involve a large number of parameters which may underconstrain the framework. Our model predicts that reward system adaptations account for mood stabilization, whereas antireward system adaptations delineate mood improvement and reduction in drug consumption. This investigation provides formal arguments encouraging current rehabilitation therapies to include meditation-like practices along with pharmaceutical drugs and behavioral counseling.
Cannabinoids are widely abused drugs. Here we show that chronic administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the active psychotropic agent in marijuana and hashish, at 1.5 mg per ...kg per day intraperitoneally for 7 days, increases the expression, at both mRNA and protein levels, of brain-derived neurotrophic factor (BDNF), in specific rat brain areas, notably in those involved in reward and addiction. Real-time PCR revealed a 10-fold up-regulation of BDNF mRNA in the nucleus accumbens (NAc) upon chronic Delta(9)-THC treatment, but there was no change at 3 or 24 h after a single injection. Smaller increases in mRNA levels were found in the ventral tegmental area (VTA), medial prefrontal cortex and paraventricular nucleus (PVN). Immunohistochemistry showed large increases in BDNF-stained cells in the NAc (5.5-fold), posterior VTA (4-fold) and PVN (1.7-fold), but no change was observed in the anterior VTA, hippocampus or dorsal striatum. Altogether, our study indicates that chronic exposure to Delta(9)-THC up-regulates BDNF in specific brain areas involved with reward, and provides evidence for different BDNF expression in the anterior and posterior VTA. Moreover, BDNF is known to modulate synaptic plasticity and adaptive processes underlying learning and memory, leading to long-term functional and structural modification of synaptic connections. We suggest that Delta(9)-THC up-regulation of BDNF expression has an important role in inducing the neuroadaptive processes taking place upon exposure to cannabinoids.
Environmental risk factors together with genetic vulnerability create a complex background to develop depression.
We investigated the associations between COMT Val
158Met and depression in a Swedish ...population-based sample of 405 depressed individuals (major depression diagnosis, dysthymia or mixed anxiety depression defined according to DSM-IV) and 2,151 healthy controls. We also analyzed interaction between this genetic variation and some environmental risk factors for depression and the link between this polymorphism and the low motivational level and negative mood state found in depressed individuals.
Depressed individuals displayed a higher frequency of the Met/Met and Met/Val genotypes compared to controls (OR
=
1.49, CI
95%
=
1.11–2.00, P
=
0.009). The association was found among men only (OR
=
2.26, CI
95%
=
1.26–4.05, p
=
0.008). Regression analysis including some potential risk factors for depression, did further indicate that Met/Met and Met/Val were associated with depression in men (P
=
0.005). There was also an interaction between genotype and family childhood problems (RERI
=
0.876, CI
95%
=
0.090–1.662 and AP
=
0.426, CI
95%
=
0.030–0.821). Further, depressed men homozygous for the Val-allele, had a higher motivational level than depressed men with a Met-variant (P
=
0.02).
The sample size of depressed individuals per group when stratifying cases according to gender and genotypes is considered a limitation.
The Met-variants of COMT Val
158Met are risk variants for depression and low motivational level in depressed Swedish men, but not women. Individuals with this risk variant in combination with a problematic childhood, have an even higher risk to develop depression.
Changes in the extracellular concentration of dopamine (DA) in the nucleus accumbens (NAc) shell and the basolateral amygdala (BLA) resulting from the voluntary ingestion of either corn oil, mineral ...oil, or 1% linoleic acid diluted with mineral oil as a vehicle were measured in rats by using in vivo microdialysis after they had been trained to establish a preference for corn oil. Ingesting the mineral oil caused no significant change in DA level in the NAc shell, whereas corn oil ingestion significantly increased the DA level during 0-15 min of the test session, reaching the maximum level of 129.8 ± 6.2% compared with the baseline after 10 min. Ingesting linoleic acid also resulted in a significant increase in DA level during 0-20 min, reaching 125.9 ± 9.0% after 10 min. Similar results were obtained in the BLA. Despite its very low calorie content, a low concentration of non-esterified fatty acid increased the DA levels equivalent to those resulting from corn oil in the brain's reward system.
Existing evidence suggests that reward and attentional networks function in concert and that activation in one system influences the other in a reciprocal fashion; however, the nature of these ...influences remains poorly understood. We therefore developed a three‐component task to assess the interaction effects of reward anticipation and conflict resolution on the behavioral performance and the activation of brain reward and attentional systems. Sixteen healthy adult volunteers aged 21–45 years were scanned with functional magnetic resonance imaging (fMRI) while performing the task. A two‐way repeated measures analysis of variance (ANOVA) with cue (reward vs. non‐reward) and target (congruent vs. incongruent) as within‐subjects factors was used to test for main and interaction effects. Neural responses to anticipation, conflict, and reward outcomes were tested. Behaviorally there were main effects of both reward cue and target congruency on reaction time. Neuroimaging results showed that reward anticipation and expected reward outcomes activated components of the attentional networks, including the inferior parietal and occipital cortices, whereas surprising non‐rewards activated the frontoinsular cortex bilaterally and deactivated the ventral striatum. In turn, conflict activated a broad network associated with cognitive control and motor functions. Interaction effects showed decreased activity in the thalamus, anterior cingulated gyrus, and middle frontal gyrus bilaterally when difficult conflict trials (e.g., incongruent targets) were preceded by reward cues; in contrast, the ventral striatum and orbitofrontal cortex showed greater activation during congruent targets preceded by reward cues. These results suggest that reward anticipation is associated with lower activation in attentional networks, possibly due to increased processing efficiency, whereas more difficult, conflict trials are associated with lower activity in regions of the reward system, possibly because such trials are experienced as less rewarding.
Motivation and effortful control interact to produce behavioral changes, but the precise nature of these interactions remains unclear. Our results suggest that rewards that are interpreted as “easy” may be associated with greater cognitive effort to maximize profit in a money‐winning paradigm.
Neuroimaging studies have been crucial in understanding changes in the various neurotransmitter systems implicated in addiction in the living human brain. Predominantly reduced striatal dopamine ...transmission appears to play an important role in psychostimulant, alcohol and heroin addiction, while addiction to cannabis may be mediated primarily by the endocannabinoid system. However, the study of other neurotransmitter systems likely involved in addiction, for example glutamate, has been limited by the number and quality of available radiotracers, and data on changes in these systems in the most common addictions are emerging only now. Further studies are needed to understand fully how the interplay of various neurotransmitter systems contributes to addiction and to ultimately help to develop more effective treatment approaches.
Alcohol exerts numerous pharmacological effects through its interaction with various neurotransmitters and neuromodulators. Among the latter, the endogenous opioids play a key role in the rewarding ...(addictive) properties of ethanol. Three types of opioid receptors (mu, delta and kappa) represent the respective targets of the major opioid peptides (beta-endorphin, enkephalins and dynorphins, respectively). The rewarding (reinforcing) properties of mu- and delta-receptor ligands are brought by activation of the mesolimbic dopamine system which ascends from the ventral tegmentum of the midbrain (VTA) to rostral structures; of these, the nucleus accumbens (NAC) is of particular importance in drug addiction. In contrast, dysphoria results from activation of kappa-receptors. The neurochemical manifestations of these opposing effects are, respectively, increases and decreases in dopamine release in the NAC. Several lines of evidence indicate that alcohol interferes with endogenous opioid mechanisms which are closely linked with dopamine transmission in the mesolimbic pathway. The view that condensation products of dopamine and alcohol-derived aldehyde (tetrahydroisoquinolines) play a role remains controversial. There is, however, much information on the direct (acute and chronic) effects of alcohol on the binding properties of opioid receptors, as well as modulation of opioid peptide synthesis and secretion (e.g. a suggested increase in beta-endorphin release). In view of the reinforcing properties of alcohol, it is relevant to consider behavioural studies involving alcohol self-administration in rodents and primates. Low doses of morphine have been found to increase, and higher doses of the opiate to decrease, alcohol consumption. Conversely, opioid antagonists such as naloxone and naltrexone (which bind to non-selectively opioid receptors) have been shown to decrease alcohol consumption under various experimental conditions. Similar results have been reported when selective mu- or delta-receptor antagonists are administered. Results obtained in genetic models of high preference for alcohol also support the view that alcohol intake depends on the activity of the endogenous opioid reward system and that alcohol consumption may serve to compensate for inherent deficits in this system. One hypothetical model proposes that reward results from activation of mu-opioid receptors in the VTA and/or delta-receptor in the NAC; both these nuclei are targets of endogenous beta-endorphin. It is suggested that alcohol interferes with this reward pathway either directly or indirectly. The available experimental data accord well with those obtained from clinical studies which opioid antagonists have been used to prevent relapse in alcoholics. Conceptual considerations concerning communalities between various forms of addictions are also discussed in this review.
SUMMARY
Background: Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical ...urgency to develop more effective treatments. Objectives: To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. Methods: We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause‐correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. Results: Preliminary findings appear to support the cause‐correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. Conclusions: PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitive–behavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects.
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