The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice

Valero, Elina; Gómez-Milanés, Iván; Almela, Pilar; Couto, Bruno Ribeiro Do; Laorden, M. Luisa; Milanés, M. Victoria; Núñez, Cristina

doi:10.1016/j.pnpbp.2018.01.018

Cited by 21 publications

(20 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably also, some naloxone CPA remained detectable in both situations (naïve and morphine-dependent). The latter observation is in accordance with the notion that other brain sites may be engaged in this response, as proposed for basolateral amygdala [48,49] or lateral Hb [50].…”

Section: Discussionsupporting

confidence: 91%

Mu opioid receptors in the medial habenula contribute to naloxone aversion

Boulos

Hamida

Bailly

et al. 2019

Neuropsychopharmacol.

View full text Add to dashboard Cite

The medial habenula (MHb) is considered a brain center regulating aversive states. The mu opioid receptor (MOR) has been traditionally studied at the level of nociceptive and mesolimbic circuits, for key roles in pain relief and reward processing. MOR is also densely expressed in MHb, however, MOR function at this brain site is virtually unknown. Here we tested the hypothesis that MOR in the MHb (MHb-MOR) also regulates aversion processing. We used chnrb4-Cre driver mice to delete the Oprm1 gene in chnrb4-neurons, predominantly expressed in the MHb. Conditional mutant (B4MOR) mice showed habenula-specific reduction of MOR expression, restricted to chnrb4-neurons (50% MHb-MORs). We tested B4MOR mice in behavioral assays to evaluate effects of MOR activation by morphine, and MOR blockade by naloxone. Locomotor, analgesic, rewarding, and motivational effects of morphine were preserved in conditional mutants. In contrast, conditioned place aversion (CPA) elicited by naloxone was reduced in both naïve (high dose) and morphine-dependent (low dose) B4MOR mice. Further, physical signs of withdrawal precipitated by either MOR (naloxone) or nicotinic receptor (mecamylamine) blockade were attenuated. These data suggest that MORs expressed in MHb B4-neurons contribute to aversive effects of naloxone, including negative effect and aversive effects of opioid withdrawal. MORs are inhibitory receptors, therefore we propose that endogenous MOR signaling normally inhibits chnrb4-neurons of the MHb and moderates their known aversive activity, which is unmasked upon receptor blockade. Thus, in addition to facilitating reward at several brain sites, tonic MOR activity may also limit aversion within the MHb circuitry.

show abstract

Section: Discussionsupporting

confidence: 91%

Mu opioid receptors in the medial habenula contribute to naloxone aversion

Boulos

Hamida

Bailly

et al. 2019

Neuropsychopharmacol.

View full text Add to dashboard Cite

show abstract

“…This pattern of morphine administration, which involves ascending drug doses, has been used extensively to study opioid tolerance and dependence . The doses of morphine were selected based in previous studies from our laboratory . The chronic saline‐treated groups were administered with saline (i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…or its vehicle (Tween 80, 10%) were acutely injected, and 30 minutes later, naloxone was administered subcutaneously (s.c.) at a dose of 1 mg/kg, in order to precipitate the morphine withdrawal syndrome, and mice were immediately confined to one of the chambers during 18 minutes. The dose of naloxone was selected based in previous studies from our laboratory . On day 5, CPA expression was tested in a drug‐free state (posttest).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Conditioned aversive memory associated with morphine withdrawal increases brain‐derived neurotrophic factor in dentate gyrus and basolateral amygdala

et al. 2019

View full text Add to dashboard Cite

Morphine has been shown to increase the expression of brain‐derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of conditioned naloxone‐precipitated morphine withdrawal on BDNF and its precursor protein, proBDNF. We used the conditioned place aversion (CPA) paradigm to evaluate the role of corticotropin‐releasing factor (CRF)/CRF1 receptor signaling on the BDNF expression and corticosterone plasma levels after CPA expression and extinction. Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone‐associated compartment. The expression of BDNF and proBDNF in the dentate gyrus (DG) and basolateral amygdala (BLA) was measured in parallel with the corticosterone plasma levels with and without CRF1 receptor blockade. Mice subjected to conditioned naloxone‐induced morphine withdrawal showed an increased expression of BDNF (in DG and BLA) in parallel with an enhancement of corticosterone plasma levels. These results demonstrated that BDNF expression together with the increased activity of hypothalamic‐pituitary‐adrenocortical (HPA) axis are critical to the acquisition of aversive memory. However, we have observed a decrease in corticosterone plasma levels and BDNF expression after CPA extinction reaffirming the importance of BDNF in the maintenance of aversive memory. In addition, the pre‐treatment with the CRF1 receptor antagonist CP‐154 526 before naloxone conditioning session impaired morphine withdrawal‐induced aversive memory acquisition, the increased corticosterone plasma levels, and the expression of BDNF observed after CPA expression in the DG and BLA. Altogether, present results are suggesting a clear connection between HPA axis and BDNF in the formation and extinction of aversive memory.

show abstract

“…Previous studies found that the basolateral amygdala (BLA) played an important role in the conditioned context-induced retrieval of morphine withdrawal memory ( Lovaglio et al, 2010 ; Garcia-Perez et al, 2016 ; Valero et al, 2018 ; Song et al, 2019 ). However, how conditioned context activates the BLA to participate in conditioned context-induced retrieval of morphine withdrawal memory remains to be unknown.…”

Section: Introductionmentioning

confidence: 99%

A Conditioning-Strengthened Circuit From CA1 of Dorsal Hippocampus to Basolateral Amygdala Participates in Morphine-Withdrawal Memory Retrieval

Cao

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

Conditioned context-induced retrieval of drug withdrawal memory contributes to drug relapse. The basolateral amygdala (BLA) is an important brain region that is involved in conditioned context-induced retrieval of morphine withdrawal memory. However, the upstream pathways of the activation of the BLA by conditioned context remains to be studied. The present results show that the CA1 of dorsal hippocampus is an upstream brain region of the activation of the BLA during conditioned context-induced morphine withdrawal memory retrieval; the indirect connection from the CA1 of dorsal hippocampus to the BLA is enhanced in mice with conditioned place aversion (CPA); the postrhinal cortex (POR) is a brain region that connects the CA1 of dorsal hippocampus and the activation of the BLA during conditioned context-induced retrieval of morphine-withdrawal memory. These results suggest that a conditioning-strengthened indirect circuit from the CA1 of dorsal hippocampus to the BLA through the POR participates in morphine withdrawal memory retrieval.

show abstract

The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice

Cited by 21 publications

References 76 publications

Mu opioid receptors in the medial habenula contribute to naloxone aversion

Mu opioid receptors in the medial habenula contribute to naloxone aversion

Conditioned aversive memory associated with morphine withdrawal increases brain‐derived neurotrophic factor in dentate gyrus and basolateral amygdala

A Conditioning-Strengthened Circuit From CA1 of Dorsal Hippocampus to Basolateral Amygdala Participates in Morphine-Withdrawal Memory Retrieval

Contact Info

Product

Resources

About