Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors

Abstract

The functional interplay between the corticolimbic GABAergic and opioidergic systems plays a crucial role in regulating the reward system and cognitive aspects of motivational behaviors leading to the development of addictive behaviors and disorders. This review provides a summary of the shared mechanisms of GABAergic and opioidergic transmission, which modulate the activity of dopaminergic neurons located in the ventral tegmental area (VTA), the central hub of the reward mechanisms. This review comprehensively covers the neuroanatomical and neurobiological aspects of corticolimbic inhibitory neurons that express opioid receptors, which act as modulators of corticolimbic GABAergic transmission. The presence of opioid and GABA receptors on the same neurons allows for the modulation of the activity of dopaminergic neurons in the ventral tegmental area, which plays a key role in the reward mechanisms of the brain. This colocalization of receptors and their immunochemical markers can provide a comprehensive understanding for clinicians and researchers, revealing the neuronal circuits that contribute to the reward system. Moreover, this review highlights the importance of GABAergic transmission-induced neuroplasticity under the modulation of opioid receptors. It discusses their interactive role in reinforcement learning, network oscillation, aversive behaviors, and local feedback or feedforward inhibitions in reward mechanisms. Understanding the shared mechanisms of these systems may lead to the development of new therapeutic approaches for addiction, reward-related disorders, and drug-induced cognitive impairment.

Brain-Region-Specific Genes Form the Major Pathways Featuring Their Basic Functional Role: Their Implication in Animal Chronic Stress Model

“…We also observe the specific elevation of glutamate neurotransmitters expression rate in losers’ hippocampus and dorsal striatum regions (orange circles) while GABAergic emission in Medium Spiny Neurons (MSN) of striatum was correspondingly lowered (blue circle). Notably, there is an observation that GABAergic neurons emission is modulated with opiodergic signaling, reported in a recent survey [ 14 ], in particular in VTA afferent.…”

Gut Microbiome-Mediated Mechanisms in Alleviating Opioid Addiction with Aqueous Extract of Anacyclus pyrethrum

“…Moreover, it has been demonstrated, through the use of opioid antagonists, that the antinociceptive effect of AEAP is partially mediated by opioid receptors [ 1 ]. Additionally, research has shown that the primary phytoconstituents present in AEAP roots are alkylamides [ 63 ], which are responsible for modulating opioidergic, serotoninergic, and GABAergic systems [ 61 ].The interaction between the opioid and GABAergic systems is crucial for understanding the rewarding and anxiolytic effects of opioids, as well as the processes involved in the development of opioid tolerance, dependence, and withdrawal [ 64 ]. We hypothesize that AEAP acts as a partial antagonist for opioids and GABAergic receptors, which could potentially explain the observed effects.…”

Assessment of Toxicity and Biological Effects of α-Pinene on Morphine Tolerance and Dependence in Mice

“…With this in mind, previous studies have demonstrated that the GABAergic system performs a pivotal function in opioid addiction. Moreover, studies have shown that positive modulators on the benzodiazepine site in the GABAA receptors (e.g., diazepam) and selective GABAA receptor agonists (e.g., muscimol) pacify morphine withdrawal signs (6,19,20,27).…”

“…Morphine dependence is associated with ailments such as anxiety, abdominal pain, diarrhea, etc. Earlier studies have shown that the continuous use of morphine affects the mesolimbic dopaminergic system in the ventral tegmental area (VTA) and leads to the development of tolerance and dependence (5,6). In this regard, studies have shown that several neural systems, such as the GABAergic and opioidergic systems, modulate the activity of the dopaminergic system, contributing to opioid tolerance and dependence (5,6).…”