Parallel buprenorphine phMRI responses in conscious rodents and healthy human subjects.
Pharmacological magnetic resonance imaging (phMRI) is one method by which a drug's pharmacodynamic effects in the brain can be assessed. Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined. In the current investigation, we aimed to build on recent clinical work in which the functional response to 0.1 and 0.2 mg/70 kg i.v. buprenorphine (partial µ-opioid receptor agonist) was measured in healthy humans. Here, we measured the phMRI response to 0.04 and 0.1 mg/kg i.v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species. PhMRI of 0.04 and 0.1 mg/kg i.v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum. Similar dose-dependent phMRI activation was observed in the human phMRI studies. These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia. This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development.
Imaging Consortium for Drug Development, P.A.I.N. Group, Harvard Medical School, Children’s Hospital of Boston, Waltham, Massachusetts 02453, USA. Lino.Becerra@childrens.harvard.edu
Lino
L
Becerra
Jaymin
J
Upadhyay
Pei-Ching
PC
Chang
James
J
Bishop
Julie
J
Anderson
Richard
R
Baumgartner
Adam J
AJ
Schwarz
Alexandre
A
Coimbra
Diana
D
Wallin
Lauren
L
Nutile
Edward
E
George
Gary
G
Maier
Soujanya
S
Sunkaraneni
Smriti
S
Iyengar
Jeffrey L
JL
Evelhoch
David
D
Bleakman
Richard
R
Hargreaves
David
D
Borsook
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping / Q000379:methods; D002047:Buprenorphine / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D008297:Male; D009488:Neurosciences / Q000295:instrumentation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists; D013045:Species Specificity
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D002047:Buprenorphine