Regulation of Human Affective Responses by Anterior Cingulate and Limbic µ-Opioid Neurotransmission

Zubieta, Jon Kar; Ketter, Terence A.; Bueller, Joshua A.; Xu, Yanjun; Kilbourn, Michael R.; Young, Elizabeth A.; Koeppe, Robert A.

doi:10.1001/archpsyc.60.11.1145

Cited by 363 publications

(310 citation statements)

References 76 publications

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“…In this sense, it has been recently shown that stress, related to certain suicidal behaviors, induces increases in m-opioid receptor mRNA expression in the rat brain (Yamamoto et al, 2003). In addition, positron emission tomography studies in humans demonstrate the in vivo involvement of these receptors in mood and behavior, further suggesting their potential implication in suicide behaviors (Zubieta et al, 2003).…”

Section: Altered Expression Of L-opioid Receptors In the Brains Of Sumentioning

confidence: 99%

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

Escribá

Ozaita

Garcı́a-Sevilla

2004

Neuropsychopharmacol

124

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The development of new therapies for the treatment of psychiatric disorders requires an in-depth knowledge of the molecular bases underlying these pathologies, which remain largely unknown. Alterations in adrenoceptors, serotonin receptors, and other G proteincoupled receptors (GPCRs) have been associated with suicide and depression. However, to date, there is little information about mRNA expression of the GPCRs in the frontal cortex of suicide victims. Our goal was to study the expression in the brain of these receptors. For this purpose, we measured mRNA levels by RT-PCR. We found that the expressions of a 2A -adrenoceptors, 5-HT 1A , 5-HT 2A serotonin receptors, and m-opioid receptors were elevated in the post-mortem brains of these suicide victims with respect to matched controls. Moreover, in the case of a 2A -adrenoceptors (the only for which these data were available), a significant correlation was observed between the level of mRNA and protein quantified in the brain of the same subjects, indicating that protein synthesis of this receptor was not influenced by post-translational regulatory mechanisms. In addition, the degree of adrenoceptor and 5-HT receptor expressions appeared to be correlated in the brains of suicide victims and control subjects. Alterations in the expression of adrenoceptors, serotonin, and opioid receptors indicate that these signaling proteins might be related to the etiopathology of suicidal and depressive behaviors. Alternatively, such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations. The results also suggest that these receptors could share common regulatory mechanisms.

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Section: Altered Expression Of L-opioid Receptors In the Brains Of Sumentioning

confidence: 99%

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

Escribá

Ozaita

Garcı́a-Sevilla

2004

Neuropsychopharmacol

124

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“…In particular, opioid release in cortical regions involved in emotional processing appears to suppress the emotive element of pain (Zubieta et al, 2001) and affective states such as sadness (Zubieta et al, 2003), whereas blocking µ-opioid receptors with naloxone increases activity in these regions (Borras et al, 2004). Thus, activation of the endogenous opioid system during psychological stress could suppress the affective and sensory components of pain independently.…”

Section: Introductionmentioning

confidence: 99%

Negative affect, pain and sex: The role of endogenous opioids

Frew

Drummond

2007

Pain

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Opioid neurotransmission modulates pain and negative affect during psychological stress.To determine whether these effects differ between men and women, the opioid receptor antagonist naltrexone or placebo was administered double-blind to 21 men and 22 women before they completed 30 minutes of difficult mental arithmetic. To heighten negative affect, participants received seven moderately noxious electric shocks during the math task, which were believed to be contingent upon performance. Before and after the math task, participants rated pain intensity and unpleasantness while their left hand was immersed in 2 o C water for up to 4 minutes. Anxiety, discouragement and anger were also rated before, during and after the math task. Tolerance of cold-induced pain was greater in men, whereas discouragement during the math task was greater in women. Opioid blockade did not influence ratings of negative affect, which increased in line with the intensity and unpleasantness of shock-induced pain. The intensity and unpleasantness of cold-induced pain increased after the math task only in women administered naltrexone.Within the naltrexone condition, pain ratings increased most in the most discouraged subjects. However, this relationship was absent in placebo recipients, implying that the hyperalgesic effect of psychological distress was tempered by opioid release. Greater stress-evoked discouragement in women than men may explain why cold-induced pain increased after the math task only in women administered naltrexone.

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“…This basic set of theoretical notions finds strong validation in the fact that opioids modulate pain and reward satiety (two very ancient homeostatic operations, presumably preceding the classic emotional primes in evolution), while in more complex and extended mammalian brains, opioids also modulate social bonding, play and separation distress (all critical emotional operations of a highly social brain). Both play and quieter forms of social comfort are high opioidergic states, while separation distress is organized in good part by the inverse condition of low opioidergic signals (validated in humans by Zubieta et al, 2003), coupled perhaps with high CRF signals. In this sense, separation distress might reflect an evolutionary extension of pain, while social comfort in a secure attachment perhaps is an evolutionary extension of a basic homeostatic wellness and satiety.…”

Section: On a Fundamental Intrinsic Relationship Between Consciousnementioning

confidence: 99%

Reflections on the neuroscientific legacy of Jaak Panksepp (1943–2017)

Watt

2017

Neuropsychoanalysis

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Regulation of Human Affective Responses by Anterior Cingulate and Limbic µ-Opioid Neurotransmission

Cited by 363 publications

References 76 publications

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

Negative affect, pain and sex: The role of endogenous opioids

Reflections on the neuroscientific legacy of Jaak Panksepp (1943–2017)

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