Functional consequences of neuropeptide FF receptors stimulation in mouse: a cerebral glucose uptake study.
The brain substrates involved in the pharmacological effects of neuropeptide FF (NPFF, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) including interactions with opioid systems, were investigated with the [14C]-2-deoxyglucose ([14C]-2-DG) autoradiography technique in mouse. The changes in cerebral activity were mapped after i.p. administration of 1DMe ([D-Tyr1,(NMe)Phe3]NPFF; 70 mg/kg), a neuropeptide FF analogue partially resistant to peptidases, alone or in combination with morphine (15 mg/kg). 1DMe induced a rapid decrease in the cerebral activity in the thalamus, the pontine reticular nuclei and the cerebellar cortex, brain regions involved in the control of motor activity and/or the processing of sensory data. This decrease, observed when 1DMe was administered 5 min before [14C]-2-DG, was reversed by morphine, which was devoid of significant effect at this time. When administered 30 min before the radioisotope, 1DMe was without effect, whereas morphine induced a significant increase in cerebral glucose utilization in the caudate putamen, the primary somatosensory cortex, the thalamus, the superior colliculus, the pontine reticular nuclei and the spinal cord. The association of morphine and 1DMe significantly increased cerebral glucose utilization in the same regions as morphine alone and also in three additional regions: the auditory cortex, the inferior colliculus and the dorsomedial periaqueductal gray. Following systemic administration, 1DMe and morphine modulated cerebral activity in brain regions involved in pain transmission and motor control, but their effects were temporally shifted, as were their effects on horizontal locomotor activity. However, neuropeptide FF-induced changes in brain activity were modulated in part by opioid receptors activation.
Quelven
I
I
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex, France.
Roussin
A
A
Zajac
J-M
JM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000378:metabolism*
D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D009020:Morphine; D003847:Deoxyglucose