Opioidergic System and Functional Architecture of Intrinsic Brain Activity: Implications for Psychiatric Disorders

Abstract

The opioidergic system and intrinsic brain activity, as organized in large-scale networks such as the salience network (SN), sensorimotor network (SMN), and default-mode network (DMN), play core roles in healthy behavior and psychiatric disorders. This work aimed to investigate how opioidergic signaling affects intrinsic brain activity in healthy individuals by reviewing relevant neuroanatomical, molecular, functional, and pharmacological magnetic resonance imaging studies in order to clarify their physiological links and changes in psychiatric disorders. The SN shows dense opioidergic innervations of subcortical structures and high expression levels of opioid receptors in subcortical-cortical areas, with enhanced or reduced activity with low or very high doses of opioids, respectively. The SMN shows high levels of opioid receptors in subcortical areas and functional disconnection caused by opioids. The DMN shows low levels of opioid receptors in cortical areas and inhibited or enhanced activity with low or high doses of opioids, respectively. Finally, we proposed a working model. Opioidergic signaling enhances SN and suppresses SMN (and DMN) activity, resulting in affective excitation with psychomotor inhibition; stronger increases in opioidergic signaling attenuate the SN and SMN while disinhibiting the DMN, dissociating affective and psychomotor functions from the internal states; the opposite occurs with a deficit of opioidergic signaling.

Dopamine D2R and opioid MOR availability in autism spectrum disorder

“…Precuneus is one of the main areas of the Default Mode Network (DMN) critically involved in social cognition and showing dysfunction in ASD [72–76]. PET studies have shown significant distribution of opioid receptors in the human DMN, and opioids modulate its activity in a dose-dependent manner as the low opioid doses inhibit and the high doses enhance it [20]. Our previous study with a largely overlapping sample revealed lower grey matter volume in the left precuneus of the ASD group [77].…”

“…There are fMRI studies demonstrating the involvement of the hippocampus in impaired perception of social emotions, as well as atypical learning, memory, and sensory hypersensitivity in ASD [78]. General ex vivo autoradiography in monkeys and humans has found a low density of MOR in the hippocampus [20]. The hippocampus is also part of the MOR-modulated DMN and has stronger functional connectivity with other DMN regions in ASD compared to controls [78].…”

“…Finally, dopamine antagonist medications such as risperidone and aripiprazole may alleviate autism symptoms, including irritability and stereotypic behavior [4][5][6]19]. The endogenous opioid system controls a wide variety of human functions, from basic homeostasis and antinociception to emotions, social attachment, and reward [9,[20][21][22][23].…”

“…The endogenous opioid system controls a wide variety of human functions, from basic homeostasis and antinociception to emotions, social attachment, and reward [9, 20–23]. Neuropeptide beta-endorphin is released from hypothalamic nuclei and mesolimbic structures, projecting to other hypothalamic and corticolimbic structures, frontal lobes, brainstem, and periaqueductal grey [9, 20]. Beta-endorphin binds to three different opioid receptors, mu-(MOR), delta-(DOR), and kappa-(KOR), which are differentially distributed across the cortical and subcortical areas.…”

The Convergent Neuroscience of Affective Pain and Substance Use Disorder

“… 83 A similar involvement of endogenous opioid signaling in salience network function is well known. 84 Alterations in the network’s connectivity are related to resting state dysfunction 85 as well as to relapse behaviors 86 in patients with OUD. More studies are needed to examine salience network activity in populations with OUD in relation to hyperalgesia symptoms, especially because pain symptoms can promote opioid craving even after months of abstinence.…”