Reversible inactivation of the dorsal hippocampus by tetrodotoxin or lidocaine: a comparative study on cerebral functional activity and motor coordination in the rat.
Reversible inactivation of the hippocampus by lidocaine or tetrodotoxin is used to investigate implications of this structure in memory processes. Crucial points related to such inactivation are the temporal and spatial extents of the blockade. We compared effects of intrahippocampal infusions of commonly-used doses of lidocaine (5 or 10 mug) or tetrodotoxin (5 or 10 ng) in rats at two post-infusion delays (5 or 30 min), using 2-deoxyglucose autoradiography to visualize local cerebral glucose metabolism, and beam-walking performance to assess motor coordination. In addition, memory retrieval was evaluated in a water maze after bilateral infusions of 10 mug lidocaine. A unilateral tetrodotoxin infusion induced dose- and time-dependent reductions of 2-deoxyglucose uptake in the vicinity of the infusion site (dorsal hippocampus: -29% to -67%) and in other ipsi- and contralateral brain regions (ventral hippocampus, lateral thalamus, cortical regions). The maximal effect was at 10 ng, at the delay of 30 min between the tetrodotoxin infusion and the 2-deoxyglucose injection. Uni- and bilateral infusions of tetrodotoxin induced dramatic motor coordination deficits. Conversely, lidocaine reduced 2-deoxyglucose uptake (-19%) in the dorsal hippocampus only at 10 mug, with weak extrahippocampal effects. Whether infused uni- or bilaterally and regardless of the dose, lidocaine did not alter motor coordination. When infused bilaterally, however, 10 microg of lidocaine impaired short-term retrieval of spatial information in a water maze. Because lidocaine i) induced a weak though significant functional blockade mainly restricted to the infusion site, ii) had no consequences on motor coordination and, nevertheless iii) altered short-term spatial memory retrieval, we conclude that acute intrahippocampal infusions of lidocaine may offer some advantages over tetrodotoxin at the doses used herein.
Pereira de Vasconcelos
A
A
LN2C FRE 2855, Université Louis Pasteur, ULP/CNRS, Institut Fédératif de Recherche IFR 37, GDR CNRS 2905, 12 rue Goethe, F 67000 Strasbourg, France.
Klur
S
S
Muller
C
C
Cosquer
B
B
Lopez
J
J
Certa
U
U
Cassel
J C
JC
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors
D000779:Anesthetics, Local; D013779:Tetrodotoxin; D008012:Lidocaine; D003847:Deoxyglucose; D005947:Glucose