Fentanyl-induced changes in brain activity in awake nonhuman primates at 9.4 Tesla.


Journal

Brain imaging and behavior
ISSN: 1931-7565
Titre abrégé: Brain Imaging Behav
Pays: United States
ID NLM: 101300405

Informations de publication

Date de publication:
Aug 2022
Historique:
accepted: 13 01 2022
pubmed: 1 3 2022
medline: 16 7 2022
entrez: 28 2 2022
Statut: ppublish

Résumé

Functional magnetic resonance imaging (fMRI) has been used to study the influence of opioids on neural circuitry implicated in opioid use disorder, such as the cortico-striatal-thalamo-cortical (CSTC) circuit. Given the increase in fentanyl-related deaths, this study was conducted to characterize the effects of fentanyl on patterns of brain activation in awake nonhuman primates. Four squirrel monkeys were acclimated to awake scanning procedures conducted at 9.4 Tesla. Subsequently, test sessions were conducted in which a dose of fentanyl that reliably maintains intravenous (IV) self-administration behavior in monkeys, 1 μg/kg, was administered and the effects on patterns of brain activity were assessed using: (1) a pharmacological regressor to elucidate fentanyl-induced patterns of neural activity, and (2) seed-based approaches targeting bilateral anterior cingulate, thalamus, or nucleus accumbens (NAc) to determine alterations in CSTC functional connectivity. Results showed a functional inhibition of BOLD signal in brain regions that mediate behavioral effects of opioid agonists, such as cingulate cortex, striatum and midbrain. Functional connectivity between each of the seed regions and areas involved in motoric, sensory and cognition-related behavior generally decreased. In contrast, NAc functional connectivity with other striatal regions increased. These results indicate that fentanyl produces changes within CSTC circuitry that may reflect key features of opioid use disorder (e.g. persistent drug-taking/seeking) and thereby contribute to long-term disruptions in behavior and addiction. They also indicate that fMRI in alert nonhuman primates can detect drug-induced changes in neural circuits and, in turn, may be useful for investigating the effectiveness of medications to reverse drug-induced dysregulation.

Identifiants

pubmed: 35226333
doi: 10.1007/s11682-022-00639-4
pii: 10.1007/s11682-022-00639-4
doi:

Substances chimiques

Fentanyl UF599785JZ

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1684-1694

Subventions

Organisme : NIDA NIH HHS
ID : T32DA015036
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047575
Pays : United States
Organisme : NIDA NIH HHS
ID : K01DA039306
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047130
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Sarah L Withey (SL)

Behavioral Biology Program, McLean Hospital - Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA. swithey@mclean.harvard.edu.

Lei Cao (L)

Behavioral Neuroimaging Laboratory, McLean Hospital - Harvard Medical School, Belmont, MA, USA.
McLean Imaging Center, McLean Hospital - Harvard Medical School, Belmont, MA, USA.

Fernando B de Moura (FB)

Behavioral Biology Program, McLean Hospital - Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.
Behavioral Neuroimaging Laboratory, McLean Hospital - Harvard Medical School, Belmont, MA, USA.
McLean Imaging Center, McLean Hospital - Harvard Medical School, Belmont, MA, USA.

Kenroy R Cayetano (KR)

McLean Imaging Center, McLean Hospital - Harvard Medical School, Belmont, MA, USA.

Michael L Rohan (ML)

McLean Imaging Center, McLean Hospital - Harvard Medical School, Belmont, MA, USA.

Jack Bergman (J)

Behavioral Biology Program, McLean Hospital - Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.

Stephen J Kohut (SJ)

Behavioral Biology Program, McLean Hospital - Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.
Behavioral Neuroimaging Laboratory, McLean Hospital - Harvard Medical School, Belmont, MA, USA.
McLean Imaging Center, McLean Hospital - Harvard Medical School, Belmont, MA, USA.

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