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Peroxisome Proliferator-Activated Receptors-Alpha Modulate Dopamine Cell Activity Through Nicotinic Receptors

BACKGROUND Modulation of midbrain dopamine neurons by nicotinic acetylcholine receptors (nAChRs) plays an important role in behavior, cognition, motivation, and reward. Specifically, nAChRs containing beta2 subunits (beta2-nAChRs) switch dopamine cells from a resting to an excited state. However, how beta2-nAChRs can be modulated and thereby how dopamine firing activity is affected remains elusive. Because changes in dopamine cell activity are reflected in the dynamics of microcircuits generating altered responses to stimuli and inputs, factors regulating their state are fundamental. Among these, endogenous ligands to the nuclear receptor-transcription factor peroxisome proliferator-activated receptors type-alpha (PPARalpha) have been recently found to suppress nicotine-induced responses of dopamine neurons. METHODS We used both in vitro and in vivo electrophysiological techniques together with behavioral analysis to investigate on the effects of modulation of PPARalpha in Sprague-Dawley rat and C57BLJ/6 mouse dopamine neurons and their interactions with beta2-nAChRs. To this aim, we took advantage of a selective reexpression of beta2-nAChR exclusively in dopamine cells by stereotaxically injecting a lentiviral vector in the mouse ventral tegmental area. RESULTS We found that activation of PPARalpha decreases in vitro both dopamine cell activity and ventral tegmental area net output through negative modulation of beta2-nAChRs. Additionally, PPARalpha activation in vivo reduces both the number of spontaneously active dopamine neurons and nicotine-induced increased locomotion. CONCLUSIONS Our combined findings suggest PPARalpha ligands as important negative modulators of beta2-nAChRs on dopamine neurons. Thus, PPARalpha ligands might prove beneficial in treating disorders in which dopamine dysfunction plays a prominent role, such as schizophrenia and nicotine addiction.

Effects of fatty acid amide hydrolase inhibition on neuronal responses to nicotine, cocaine and morphine in the nucleus accumbens shell and ventral tegmental area: involvement of PPAR-α nuclear receptors

The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N‐acylethanolamine (NAE) anandamide and the endogenous non‐cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine‐induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine‐induced drug self‐administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine‐induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine‐, cocaine‐ or morphine‐induced actions in the ShNAc. Experiments involved single‐unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1‐receptors and alpha‐type peroxisome proliferator‐activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine‐induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system.

The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity

Psychologists usually considered the “Self” as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potential forms. According to Jung, the Self originates from an inborn dynamic structure integrating the essential drives of our “brain–mind,” and leading both to instinctual behavioral actions and to archetypal psychological experiences. Interestingly, recent neuroethological studies indicate that our subjective identity rests on ancient neuropsychic processes that humans share with other animals as part of their inborn constitutional repertoire. Indeed, brain activity within subcortical midline structures (SCMSs) is intrinsically related to the emergence of prototypical affective states, that not only influence our behavior in a flexible way, but alter our conscious field, giving rise to specific feelings or moods, which constitute the first form of self-orientation in the world. Moreover, such affective dynamics play a central role in the organization of individual personality and in the evolution of all other (more sophisticated) psychological functions. Therefore, on the base of the convergence between contemporary cutting-edge scientific research and some psychological intuitions of Jung, we intend here to explore the first neuroevolutional layer of human mind, that we call the affective core of the Self.

Personality Similarity and Romantic Relationship Adjustment During the Couple Life Cycle

Over the last decade, a substantial number of studies have focused on the role of personality traits and of the personality trait similarity/dissimilarity in partner selection and in predicting the quality of adult romantic relationships. The present study contributes to this general objective by investigating the correlations between levels of similarity/dissimilarity in partners’ personality profiles, analyzed through the Big Five dimensions, and levels of romantic relationship adjustment at different stage of a couple’s life course. A sample of Italian couples (N = 92 couples; 184 individuals) completed the Big Five Questionnaire and the Dyadic Adjustment Scale. The results revealed that similarity was not directly related with romantic relationship adjustment. Similarity only affected adjustment in interaction with the length of relationship. Partners reporting high levels of similarity in conscientiousness and openness showed the highest levels of romantic relationship adjustment during the first years of their relationship, while showing lower levels of adjustment as the relationship progressed. The lower levels of romantic relationship adjustment fell within the length of relationship range spanning between 10 and 21 years. These results suggest the importance of considering the life cycle perspective when studying the impact of personality similarity on romantic relationships, as well as suggesting the need to analyze the relationship between personality factors and interpersonal processes in a deeper way particularly in counseling and therapeutic contexts.

La percezione di sicurezza nell'attaccamento : un'analisi delle relazioni familiari attraverso Il social relations model

Il presente studio e volto a rilevare la natura relazionale della percezione della sicurezza nell’attaccamento all’interno dei sistemi familiari attraverso l’utilizzo del Social Relations Model (Kenny, 2005) e la rilevazione dei cosiddetti effetti gruppo, attore, partner e relazione. Al campione, costituito da 50 famiglie di 4 membri, e stata somministrata l’Adult Attachment Scale (Collins e Read, 1990) adattata per la raccolta di dati diadici. I risultati ottenuti, oltre ad offrire una prima stima della potenzialita del SRM nel cogliere le dinamiche relazionali della famiglia, consentono di riflettere criticamente sui suoi possibili ambiti di applicazione.

Analytical ethnopsychology, psyche and politics

This article examines some basic premises of analytical psychology from the perspective of ethnopsychology. The creation of a Jungian ethnopsychological group in Italy has ignited the revisiting of the central therapeutic procedures of the basic Jungian model as well developing some reflections. Some of the themes this article addresses include the analytical relationship within an ethnopsychological context, the re-evaluation of the Persona, the relationship between analysis, anthropology and politics, the relationship between interpretation and amplification, and the use of archetypal material with patients from different socio–cultural backgrounds.

Effects of fatty acid amide hydrolase inhibition on neuronal responses to nicotine, cocaine and morphine in the nucleus accumbens shell and ventral tegmental area: involvement of PPAR-α nuclear receptors: FAAH inhibition on neuronal responses

The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N‐acylethanolamine (NAE) anandamide and the endogenous non‐cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine‐induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine‐induced drug self‐administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine‐induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine‐, cocaine‐ or morphine‐induced actions in the ShNAc. Experiments involved single‐unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1‐receptors and alpha‐type peroxisome proliferator‐activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine‐induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system.

PRECLINICAL STUDY: FULL ARTICLE: Effects of fatty acid amide hydrolase inhibition on neuronal responses to nicotine, cocaine and morphine in the nucleus accumbens shell and ventral tegmental area: involvement of PPAR‐α nuclear receptors

The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N‐acylethanolamine (NAE) anandamide and the endogenous non‐cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine‐induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine‐induced drug self‐administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine‐induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine‐, cocaine‐ or morphine‐induced actions in the ShNAc. Experiments involved single‐unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1‐receptors and alpha‐type peroxisome proliferator‐activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine‐induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system.

T11-P-03 Towards the deconstruction of gender role categories: a critical analysis of the ACL scales of measure for masculine and feminine orientation

Objective This is a critical reflection on the Adjective Check List scales of measure for masculine (Mas) and feminine (Fem) orientation (Gough et al., 1981), based on a sample of Italian homosexuals (45 males and 52 females). Method The researchs design of a factorial type among the subjects with a non-equivalent control group (43 heterosexual males and 49 heterosexual females). In the attempt to verify the hypothetical existence of gender crossed characteristics of male and female homosexual orientation (elevated scores to the Fem for the homosexual males and elevated scores to the Mas for the homosexual females) - as it is highlighted in the literature of reference it has been possible, through a factorial Manova 2×2 carried out on the dimensions under analysis (with sex and sexual orientation as between factors) to find the stereotypical nature of the adjectives which are part of the scales. Results The study broadens the reflections on the acquisition process of sexual identity regarding gender and role constructions which appear to be related not only to the childhood, but also to complex interpersonal affective regulation processes. Conclusion The research considers the possibility of modernization and updating of the existing methods of measure, which are old-fashioned and therefore little sensitive at understanding the social-relational and affective transformations that involve the personality scales under examination.