The effect of neuropeptide FF in the amygdala kindling model.
OBJECTIVE
Neuropeptide FF (NPFF) and its receptors (NPFF1 R and NPFF2 R) are differentially distributed throughout the central nervous system. NPFF reduces cortical excitability in rats when administered intracerebroventricularly (i.c.v.), and both NPFF and NPFF1 R antagonists attenuate pilocarpine-induced limbic seizures. In this study, our aim was to determine whether NPFF exerts anticonvulsant or anti-epileptogenic effects in the rat amygdala kindling model for temporal lobe seizures.


METHODS
Male Wistar rats were implanted with a recording/stimulation electrode in the right amygdala and a cannula in the left lateral ventricle. In a first group of animals, the afterdischarge threshold (ADT) was determined after a single i.c.v. infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; n = 10). Subsequently, daily infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; i.c.v.; n = 9) was performed, followed by a kindling stimulus (ADT+200 μA). Afterdischarge duration and seizure severity were evaluated after every kindling stimulus. A second group of rats (n = 7) were fully kindled, and the effect of saline or a high dose of NPFF (10 nmol/h for 2 h, i.c.v.) on ADT and the generalized seizure threshold (GST) was subsequently determined.


RESULTS
In naive rats, NPFF significantly increased the ADT compared to control (435 ± 72 μA vs 131 ± 23 μA [P < 0.05]). When rats underwent daily stimulations above the ADT, NPFF did not delay or prevent kindling acquisition. Furthermore, a high dose of NPFF did not alter ADT or GST in fully kindled rats.


CONCLUSIONS
I.c.v. administration of NPFF reduced excitability in the amygdala in naive, but not in fully kindled rats, and had no effect on kindling acquisition.
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
I
I
Buffel
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
A
A
Meurs
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.|Center for Neurosciences, Department of Pharmaceutical Chemistry, Drug Analysis & Drug information, University of Brussels, Brussels, Belgium.
J
J
Portelli
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
R
R
Raedt
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
V
V
De Herdt
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
L
L
Poppe
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
V
V
De Meulenaere
Swammerdam Institute of Life Sciences, Department of Neurobiology, University of Amsterdam, Amsterdam, The Netherlands.
W
W
Wadman
Therapeuthic Innovation Laboratory, Faculty of Pharmacy, UMR 7200, CNRS, University of Strasbourg, Illkirch Graffenstaden, France.
F
F
Bihel
Therapeuthic Innovation Laboratory, Faculty of Pharmacy, UMR 7200, CNRS, University of Strasbourg, Illkirch Graffenstaden, France.
M
M
Schmitt
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
K
K
Vonck
Therapeuthic Innovation Laboratory, Faculty of Pharmacy, UMR 7200, CNRS, University of Strasbourg, Illkirch Graffenstaden, France.
J-J
JJ
Bourguignon
Research Institute of ESBS, CNRS, UMR7242, University of Strasbourg, Illkirch, France.
F
F
Simonin
Center for Neurosciences, Department of Pharmaceutical Chemistry, Drug Analysis & Drug information, University of Brussels, Brussels, Belgium.
I
I
Smolders
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent University Hospital, Ghent, Belgium.
P
P
Boon
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy*; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D009842:Oligopeptides; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
afterdischarge threshold; amygdala kindling model; generalized seizure threshold; kindling acquisition; neuropeptide FF