title: A method for conducting functional MRI studies in alert nonhuman primates: initial results with opioid agonists in male cynomolgus monkeys.
abstract: Functional MRI (fMRI) has emerged as a powerful technique for assessing neural effects of psychoactive drugs and other stimuli. Several experimental approaches have been developed to use fMRI in anesthetized and awake animal subjects, each of which has its advantages and complexities. We sought to assess whether one particular method to scan alert postanesthetized animals can be used to assess fMRI effects of opioid agonists. To date, the use of fMRI as a method to compare pharmacological effects of opioid drugs has been limited. Such studies are important because mu and kappa opioid receptor agonists produce distinct profiles of behavioral effects related both to clinically desirable endpoints (e.g., analgesia) and to undesirable effects (e.g., abuse potential). This study sought to determine whether we could use our fMRI approach to compare acute effects of behaviorally equipotent (3.2 μg/kg) intravenous doses of fentanyl and U69,593 (doses that do not affect cardiorespiratory parameters). Scans were acquired in alert male cynomolgus macaques acclimated to undergo fMRI scans under restraint, absent excessive stress hormone increases. These opioid agonists activated bilateral striatal and nucleus accumbens regions of interest. At the dose tested, U69,593 induced greater left nucleus accumbens BOLD activation than fentanyl, while fentanyl activated left dorsal caudate nucleus more than U69,593. Our results suggest that our fMRI approach could be informative for comparing effects of opioid agonists.
authors.affiliation: McLean Imaging Center, McLean Hospital, Belmont, MA 02478, USA. kaufman@mclean.harvard.edu
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Kaufman
authors.forename: Amy C
authors.initials: AC
authors.lastname: Janes
authors.forename: Blaise deB
authors.initials: Bd
authors.lastname: Frederick
authors.forename: Melanie
authors.initials: M
authors.lastname: Brimson-Théberge
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Tong
authors.forename: Samuel B
authors.initials: SB
authors.lastname: McWilliams
authors.forename: Ashley
authors.initials: A
authors.lastname: Bear
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Gillis
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Schrode
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D003213:Conditioning, Psychological; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008252:Macaca fascicularis / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000009:adverse effects / Q000662:veterinary*; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D012149:Restraint, Physical / Q000009:adverse effects / Q000662:veterinary; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology; D014851:Wakefulness
chemical_list: D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D000324:Adrenocorticotropic Hormone; C045444:U 69593; D005283:Fentanyl; D006854:Hydrocortisone