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1 |
The Negative Affect of Protracted Opioid Abstinence: Progress and Perspectives From Rodent Models
تأثیر منفی پرهیز از مصرف مواد افیونی طولانی: پیشرفت و چشم انداز مدل های جوندگان-2020 Opioid use disorder (OUD) is characterized by the development of a negative emotional state that develops after a
history of long-term exposure to opioids. OUD represents a true challenge for treatment and relapse prevention.
Human research has amply documented emotional disruption in individuals with an opioid substance use disorder, at
both behavioral and brain activity levels; however, brain mechanisms underlying this particular facet of OUD are only
partially understood. Animal research has been instrumental in elucidating genes and circuits that adapt to long-term
opioid use or are modified by acute withdrawal, but research on long-term consequences of opioid exposure and their
relevance to the negative affect of OUD remains scarce. In this article, we review the literature with a focus on two
questions: 1) Do we have behavioral models in rodents, and what do they tell us? and 2) What do we know about the
neuronal populations involved? Behavioral rodent models have successfully recapitulated behavioral signs of the
OUD-related negative affect, and several neurotransmitter systems were identified (i.e., serotonin, dynorphin,
corticotropin-releasing factor, oxytocin). Circuit mechanisms driving the negative mood of prolonged abstinence
likely involve the 5 main reward–aversion brain centers (i.e., nucleus accumbens, bed nucleus of the stria terminalis,
amygdala, habenula, and raphe nucleus), all of which express mu opioid receptors and directly respond to opioids.
Future work will identify the nature of these mu opioid receptor–expressing neurons throughout reward–aversion
networks, characterize their adapted phenotype in opioid abstinent animals, and hopefully position these primary
events in the broader picture of mu opioid receptor–associated brain aversion networks. Keywords: Mood | Mu opioid receptor (MOR) | Neural circuits | Opioid use disorder (OUD) | Opioid withdrawal | Rodent behavior |
مقاله انگلیسی |
2 |
Synaptic Specificity, Recognition Molecules, and Assembly of Neural Circuits
ویژگی سیناپسی ، مولکولهای تشخیص و مونتاژ مدارهای عصبی-2020 Developing neurons connect in specific and stereotyped ways to form the complex circuits that underlie
brain function. By comparison to earlier steps in neural development, progress has been slow
in identifying the cell surface recognition molecules that mediate these synaptic choices, but new
high-throughput imaging, genetic, and molecular methods are accelerating progress. Over the past
decade, numerous large and small gene families have been implicated in target recognition,
including members of the immunoglobulin, cadherin, and leucine-rich repeat superfamilies. We review
these advances and propose ways in which combinatorial use of multifunctional recognition
molecules enables the complex neuron-neuron interactions that underlie synaptic specificity. |
مقاله انگلیسی |
3 |
Hypothalamic Interactions with Large-Scale Neural Circuits Underlying Reinforcement Learning and Motivated Behavior
تعاملات هیپوتالاموس با مدارهای عصبی در مقیاس بزرگ زمینه یادگیری تقویتی و رفتار انگیزه ای-2020 Biological agents adapt behavior to support the survival needs of the individual
and the species. In this review we outline the anatomical, physiological, and
computational processes that support reinforcement learning (RL). We describe
two circuits in the primate brain that are linked to specific aspects of learning and
goal-directed behavior. The ventral circuit, that includes the amygdala, ventral
medial prefrontal cortex, and ventral striatum, has substantial connectivity with
the hypothalamus. The dorsal circuit, that includes inferior parietal cortex, dorsal
lateral prefrontal cortex, and the dorsal striatum, has minimal connectivity with
the hypothalamus. The hypothalamic connectivity suggests distinct roles for
these circuits. We propose that the ventral circuit defines behavioral goals, and
the dorsal circuit orchestrates behavior to achieve those goals. |
مقاله انگلیسی |