Major depression (MD) might be conceptualized as pathological under-arousal of positive affective... more Major depression (MD) might be conceptualized as pathological under-arousal of positive affective systems as parts of a network of brain regions assessing, reconciling and storing emotional stimuli versus an over-arousal of parts of the same network promoting separation-distress/GRIEF. In this context depression can be explained as an emotional pain state that is the result of a disregulation of several sub-systems that under physiological conditions are concerned with bodily or emotional homeostasis of the human organism in a social context.
Physiologically, homeostasis is maintained by influences of the SEEKING system represented – amongst others – by the medial forebrain bundle (MFB). Neuroimaging studies show that the MFB has a proven access to the GRIEF/Sadness system. A functional decoupling of these systems with a dysfunctional GRIEF pathway might result in MD. Therewith GRIEF and SEEKING/PLEASURE systems play important roles as opponents in maintenance of emotional homeostasis. Chronic electrical modulation of the reward SEEKING pathways with deep brain stimulation might show anti-depressive effects inhumanssuffering fromMDby re-initiating an emotional equilibrium (of higher or lower activity) between these opposing systems.
ABSTRACT The relative retention of 1 4C in the medial hypothalamus as compared to the lateral hyp... more ABSTRACT The relative retention of 1 4C in the medial hypothalamus as compared to the lateral hypothalamus after intragastric loads of 25 μC of d-glucose-1 4 C was attenuated by pretreatment with 2-deoxy-D-glucose. Using a similar temporal paradigm, it was also found that 2-deoxy-D-glucose prevented the satiating effects of intragastric loads of d-glucose at a point in time when the hypothalamic 1 4 C differential was attenuated. The data indicate that inhibition of feeding by glucose is correlated with greater relative retention of carbon in the medial hypothalamus than the lateral hypothalamus. When this distribution differential is attenuated then satiety is also reduced.
Calcitonin gene-related peptide in the brain: Neurochemical and behavioral investigations
Annals of the New York Academy of Sciences
CGRP in the amygdala is concentrated in an area close to the central nucleus. High potassium rele... more CGRP in the amygdala is concentrated in an area close to the central nucleus. High potassium releases CGRP, and this release, as well as the tissue concentration of CGRP in the amygdala, can be influenced by neuroleptic drugs. Both molecular forms, alpha- and beta-CGRP, are present in the amygdala in a ratio of approximately 3:1. CGRP influences social behavior in chicken. Therefore, CGRP may have a prominent role in psycho-behavioral function and may be a target for action and/or side effects of antipsychotic drugs.
Examples of application of the affective neuroscience strategy to clinical issues
In the previous chapter, I summarized how the basic pre-clinical affective neuroscience view of e... more In the previous chapter, I summarized how the basic pre-clinical affective neuroscience view of emotional organization of the mammalian brain can facilitate our understanding of human emotional feelings. In this chapter, I will look at the clinical implications of this work, which are substantial, both in the arena of new medication development as well as how we conceptualize psychiatric disorders. In 1972, it was discovered that all opioid addictions are mediated by a single receptor molecule in the brain, the mu-opioid receptor - the first neurotransmitter receptor objectively identified in the mammalian brain. If this receptor is blocked with drugs such as naloxone or naltrexone, then all the pleasurable and pain- alleviating effects of opiates from morphine to heroin are eliminated. Without this receptor, there can be no opiate addiction and the social chaos that results from abuse of powerful opiate drugs that bind to this receptor. Soon after the discovery of this receptor, it...
Cross-Species Neuroaffective Parsing of Primal Emotional Desires and Aversions in Mammals
Emotion Review
The primal motivational systems of all mammals are constituted of the evolved affective brain net... more The primal motivational systems of all mammals are constituted of the evolved affective brain networks that gauge key survival issues. However, since progress in functional neuroscience has historically lagged behind conceptual developments in psychological science, motivational processes have traditionally been anchored to behavioral rather than neural and affective issues. Attempts to retrofit neuroaffective issues onto established psychological-conceptual structures are problematic, especially when fundamental evidence for primal affective circuits, and their neural nature, comes largely from animal research. This article provides a synopsis of our growing understanding of primary-process emotional systems of mammalian brains and minds, which provides a new empirically based infrastructure for higher levels of human theorizing.
Intraoral self injection: II. The simulation of self-stimulation phenomena with a conventional reward
Psychonomic science
The behavior of animals self-injecting themselves with a highly appetitive solution was strikingl... more The behavior of animals self-injecting themselves with a highly appetitive solution was strikingly similar to behavior of animals responding for ESB. Fast extinction, priming, and extinction without responding were demonstrated. ESB data was best simulated by intraoral self-injection animals on an ad lib food schedule whose behavior was maintained by the incentive quality of the food reward.
Cal Izard has provided psychology a robust vision of human emotional feelings. He has addressed t... more Cal Izard has provided psychology a robust vision of human emotional feelings. He has addressed the full spectrum of emotional-developmental-cognitive complexities entailed in clarifying seemingly impenetrable mysteries: How do we experience emotions and how do they guide cognitive development? Izard's developmental studies of infant minds integrate the primal evolutionary affective foundations of our nature with the diverse paths of nurture, and are framed in ways that can promote human thriving. His multilayered vision of our emotional nature resonates well with modern cross-species affective neuroscience perspectives.
Rewarding and punishing properties of deep brain stimulation: The most promising entry points for constitutive studies of affective experiences in other animals...with profound psychiatric implications for human consciousness and psychiatric therapeutics
Future pre-clinical modeling of psychiatric disorders will need to take animal emotional feelings... more Future pre-clinical modeling of psychiatric disorders will need to take animal emotional feelings more seriously than in the past. In his target article, Myron Hofer summarizes a superb research program on the maternal regulation of infant physiologies, progressing toward a gradual opening of the Pandora's Box of animal affective phenomenal consciousness that may help guide development of new psychiatric treatments. In this commentary, I summarize my own long-term perspective on this critical issue, much neglected in modern behavioral neuroscience. We can indeed empirically study the primal emotional feelings of other animals because of the tight correspondence between deep-brain stimulation induced activation of emotional-instinctual behavior patterns, and the highly consistent rewarding and punishing properties of such induced states – which are evidence-based indicators of various positive and negative emotional feelings.
In rats, the rates of 20 kHz and 50 kHz ultrasonic vocalizations (USVs) can be used as a selectiv... more In rats, the rates of 20 kHz and 50 kHz ultrasonic vocalizations (USVs) can be used as a selective breeding phenotype and variations in this phenotype can be an indicator of positive affective states and developmental differences. The 50 kHz USV is elicited by positive or rewarding stimuli (e.g., food, sex, drugs of abuse) and therefore can be an indictor of a positive affective state. Conversely, the 20 kHz USV is elicited by aversive stimuli (e.g., foot shock, presence of a predator, social defeat) indicating a negative affective state. In this study, we tested the effect of selectively breeding for 50 kHz USVs on a variety of social / emotional behaviors across the animal's lifespan. These social / emotional measures consisted of observations of pup retrieval latency and maternal care behaviors, measurement of isolation distress calls and conditioned odor preference as pups (age 1-12 days), play behavior, and social investigation as juveniles (age 21-32 days) into adulthood (90+ days of age). Cross fostering was utilized to determine if the differences in behaviors were primarily a result of maternal care or genetic expression. Results indicate that animals selected for low levels of 50 kHz USVs show the greatest alterations in social behaviors compared to the random "control" line animals. The low line animals showed a slight decrease in maternal/pup bonding, increased isolation distress calls, and failed to show a preference for a maternally associated odor, a marginal decrease in dorsal contacts during rough-and-tumble play behavior, and significantly more investigation in the social investigation paradigm after isolate housing. The social behaviors of the high line animals did not consistently vary from the random line animals with the exception of more investigation iv during social port testing. Based on cross fostering results, maternal care does not appear to explain the differences observed in these selectively bred lines. These results provide implications for the study of genetics underlying emotional states, as well as contribute to the research underlying the emotional changes in developmental disorders such as autistic spectrum disorder. v "Laughter seems primarily to be the expression of mere joy or happiness." -Charles Darwin vi This manuscript is dedicated to my family, both immediate and extended, who have provided a great deal of support and encouragement during this project. vii ACKNOWLEDGMENTS First and foremost, I would like to acknowledge my advisor, H. Casey Cromwell for all of the planning and preparation that went into organizing this project, as well as the countless hours of reading and revising needed to prepare this manuscript. A sincere thank you for all of your efforts! In addition, members, Jaak Panksepp and Dara Musher-Eizenman, who served on this committee, contributed invaluable insight and expertise to this project. Their efforts are greatly appreciated.
Please cite this article in press as: Cloutier, S., et al., Playful handling of laboratory rats i... more Please cite this article in press as: Cloutier, S., et al., Playful handling of laboratory rats is more beneficial when applied before than after routine injections. Appl. Anim. Behav. Sci. (2015), http://dx.
The question of the self has intrigued philosophers and psychologists for a long time. More recen... more The question of the self has intrigued philosophers and psychologists for a long time. More recently, distinct concepts of self have also been suggested in neuroscience. However, the exact relationship between these concepts and neural processing across different brain regions remains unclear. This article reviews neuroimaging studies comparing neural correlates during processing of stimuli related to the self with those of non-self-referential stimuli. All studies revealed activation in the medial regions of our brains' cortex during self-related stimuli. The activation in these so-called cortical midline structures (CMS) occurred across all functional domains (e.g., verbal, spatial, emotional, and facial). Cluster and factor analyses indicate functional specialization into ventral, dorsal, and posterior CMS remaining independent of domains. Taken together, our results suggest that self-referential processing is mediated by cortical midline structures. Since the CMS are densely and reciprocally connected to subcortical midline regions, we advocate an integrated cortical -subcortical midline system underlying human self. We conclude that self-referential processing in CMS constitutes the core of our self and is critical for elaborating experiential feelings of self, uniting several distinct concepts evident in current neuroscience. D
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Papers by Jaak Panksepp
Physiologically, homeostasis is maintained by influences of the SEEKING system represented – amongst others – by the medial forebrain bundle (MFB). Neuroimaging studies show that the MFB has a proven access to the GRIEF/Sadness system. A functional decoupling of these systems with a dysfunctional GRIEF pathway might result in MD. Therewith GRIEF and SEEKING/PLEASURE systems play important roles as opponents in maintenance of emotional homeostasis. Chronic electrical modulation of the reward SEEKING pathways with deep brain stimulation might show anti-depressive effects inhumanssuffering fromMDby re-initiating an emotional equilibrium (of higher or lower activity)
between these opposing systems.