The SEEKING Drive and Its Fixation: A Neuro-Psycho-Evolutionary Approach to the Pathology of Addiction.

Neuro-ethological studies conducted by Panksepp and his colleagues have provided an understanding of how the activity of the mesolimbic dopaminergic (ML DA) system leads to the emotional disposition to SEEK/Explore, which is involved in all appetitive motivated behavior and mental activity. In pathological addiction phenomena, this emotional disposition "fixes" itself on certain obsessive-compulsive habits, losing its versatility and its natural predisposition to spontaneous and unconditioned activation. Overall, the result is a consistent disinterest in everything that is not the object of addiction.

The Brain Emotional Systems in Addictions: From Attachment to Dominance/Submission Systems.

Human development has become particularly complex during the evolution. In this complexity, adolescence is an extremely important developmental stage. Adolescence is characterized by biological and social changes that create the prerequisites to psychopathological problems, including both substance and non-substance addictive behaviors.

Panic disorder: attack of fear or acute attack of solitude? Convergences between affective neuroscience and phenomenological-Gestalt perspective.

There is consensus among scientists in considering Panic Attack (PA) as an exaggerated fear response triggered by intense activation of the amygdala and related Fear brain network. Current guidelines for treatment (. National Institute for Clinical Excellence, NICE, 2011), that are based on this view, do not achieve satisfactory results: one-third of all treated patients report persistent PAs and other Panic Disorder (PD) symptoms, and several meta-analyses report the high likelihood of relapse.

The "Instinct" of Imagination. A Neuro-Ethological Approach to the Evolution of the Reflective Mind and Its Application to Psychotherapy.

Recent neuro-psychoanalytic literature has emphasized the view that our subjective identity rests on ancient subcortical neuro-psychic processes expressing unthinking forms of experience, which are "affectively intense without being known" (Solms and Panksepp, 2012). Devoid of internal representations, the emotional states of our "core-Self" (Panksepp, 1998b) are entirely "projected" towards the external world and tend to be discharged through instinctual action-patterns. However, due to the close connections between the subcortical and the cortical midline brain, the emotional drives may also find a way to be reflected within an intrinsic self-referential processing, evident when the organism is not actively engaged with the external world.

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.

d-Amphetamine stimulates unconditioned exploration/approach behaviors in crayfish: towards a conserved evolutionary function of ancestral drug reward.

In mammals, rewarding properties of drugs depend on their capacity to activate a dopamine-mediated appetitive motivational seeking state--a system that allows animals to pursue and find all kinds of objects and events needed for survival. With such states strongly conserved in evolution, invertebrates have recently been developed into a powerful model in addiction research, where a shared ancestral brain system for the acquisition of reward can mediate drug addiction in many species. A conditioned place preference paradigm has illustrated that crayfish seek out environments that had previously been paired with psychostimulant and opioid administration.

The SEEKING mind: primal neuro-affective substrates for appetitive incentive states and their pathological dynamics in addictions and depression.

Appetitive motivation and incentive states are essential functions sustained by a common emotional brain process, the SEEKING disposition, which drives explorative and approach behaviors, sustains goal-directed activity, promotes anticipatory cognitions, and evokes feelings of positive excitement which control reward-learning. All such functions are orchestrated by the same "archetypical" neural processes, activated in ancient subcortical areas and transported to the forebrain by the mesolimbic dopamine (ML-DA) system. In mammals, the neurophysiology of the SEEKING urge is expressed by DA-promoted high-frequency oscillations, in the form of transient and synchronized gamma waves (>30Hz) emerging in limbic forebrain and diffusing throughout basal ganglia-thalamocortical (BG-T-C) circuits.

Drug-sensitive reward in crayfish: an invertebrate model system for the study of SEEKING, reward, addiction, and withdrawal.

In mammals, rewarding properties of drugs depend on their capacity to activate appetitive motivational states. With the underlying mechanisms strongly conserved in evolution, invertebrates have recently emerged as a powerful new model in addiction research. In crayfish natural reward has proven surprisingly sensitive to human drugs of abuse, opening an unlikely avenue of research into the basic biological mechanisms of drug addiction.

Is subcortical-cortical midline activity in depression mediated by glutamate and GABA? A cross-species translational approach.

Major depressive disorder has recently been characterized by abnormal resting state hyperactivity in anterior midline regions. The neurochemical mechanisms underlying resting state hyperactivity remain unclear. Since animal studies provide an opportunity to investigate subcortical regions and neurochemical mechanisms in more detail, we used a cross-species translational approach comparing a meta-analysis of human data to animal data on the functional anatomy and neurochemical modulation of resting state activity in depression.

Behavioral functions of the mesolimbic dopaminergic system: an affective neuroethological perspective.

The mesolimbic dopaminergic (ML-DA) system has been recognized for its central role in motivated behaviors, various types of reward, and, more recently, in cognitive processes. Functional theories have emphasized DA's involvement in the orchestration of goal-directed behaviors and in the promotion and reinforcement of learning. The affective neuroethological perspective presented here views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (SEEKING) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms.

Ethanol consumption and reward depend on norepinephrine in the prefrontal cortex.

We studied the involvement of norepinephrine in the medial prefrontal cortex in the rewarding/reinforcing effects of ethanol. We evaluated the effects of norepinephrine selective depletion in the medial prefrontal cortex of C57/BL6J inbred mice that are commonly used in molecular studies and are highly susceptible to the behavioral effects of ethanol. In mice with prefrontal norepinephrine depletion, ethanol did not induce conditioned place preference, and a clear-cut reduction of ethanol consumption and preference was evident.

Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine.

Multiple lines of evidence demonstrate that the noradrenergic system provides both direct and indirect excitatory drive onto midbrain dopamine (DA) neurons. We used DA beta-hydroxylase (DBH) knockout (Dbh-/-) mice that lack norepinephrine (NE) to determine the consequences of chronic NE deficiency on midbrain DA neuron function in vivo. Basal extracellular DA levels were significantly attenuated in the nucleus accumbens (NAc) and caudate putamen (CP), but not prefrontal cortex (PFC), of Dbh-/- mice, while amphetamine-induced DA release was absent in the NAc and attenuated in the CP and PFC.

Prefrontal cortical norepinephrine release is critical for morphine-induced reward, reinstatement and dopamine release in the nucleus accumbens.

Increasing evidence suggests that in addition to the mesoaccumbens dopamine (DA) system other neurotransmitter and brain systems are also involved in opiate addiction. Recent evidence points to a major involvement of brain norepinephrine (NE) in the behavioral and central effects of opiates and, more specifically, indicates that NE in the prefrontal cortex may have a critical role in rewarding effects of opiates. Moreover, a body of data points to regions within the medial prefrontal cortex (mpFC) acting as final common pathway of drug relapse behavior.

In vivo evidence that genetic background controls impulse-dependent dopamine release induced by amphetamine in the nucleus accumbens.

Amphetamine is known to increase dopamine (DA) release by acting directly on dopamine transporters (DAT), primarily through a mechanism that is independent of impulse flow. We present evidence to show that impulse-dependent increase in DA outflow in the nucleus accumbens (NAc) is produced by amphetamine depending on genetic background. Systemic amphetamine produced higher accumbal DA release in the widely exploited C57BL/6J background than in the DBA/2J.

Dopamine in the medial prefrontal cortex controls genotype-dependent effects of amphetamine on mesoaccumbens dopamine release and locomotion.

Mice of background DBA/2J are hyporesponsive to the behavioral effects of D-amphetamine in comparison with the widely exploited murine background C57BL/6J. In view of the important role of dopamine (DA) release in the nucleus accumbens (NAc) regarding the behavioral effects of psychostimulants, we tested the hypothesis of an inverse relationship between mesocortical and mesoaccumbens DA functioning in the two backgrounds. Systemic D-amphetamine induces a sustained increase in DA release in the medial prefrontal cortex (mpFC) accompanied by a poor increase in the NAc in mice of the low-responsive DBA/2J background, as shown by intracerebral microdialysis in freely moving animals.

Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release.

Increasing evidence points to a major involvement of cortical areas in addictive mechanisms. Noradrenergic transmission in the medial prefrontal cortex (mpFC) has been shown to affect the motor effects of amphetamine, although there is no evidence of its involvement in the rewarding effects of this psychostimulant. The present experiments were aimed at investigating the possibility of a selective involvement of prefrontal cortical norepinephrine (NE) in the rewarding-reinforcing effects of amphetamine.

Genotype- and experience-dependent susceptibility to depressive-like responses in the forced-swimming test.

Rationale: The forced-swimming test (FST) is utilized to reproduce passive coping responses to stress that may model a relevant aspect of human depression in rodent species. Animals showing high levels of passive responses to the FST are assumed to model pathologically depressed individuals.

Objectives: We evaluated sensitivity of FST-induced behavioral responses to the interaction between genetic and environmental influences.