RT Journal Article
SR Electronic
T1 Characterization of Epibatidine Binding to Medial Habenula: Potential Role in Analgesia
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 759
OP 765
DO 10.1124/jpet.102.033498
VO 302
IS 2
A1 Per Plenge
A1 Erling T. Mellerup
A1 Gitta Wörtwein
YR 2002
UL http://jpet.aspetjournals.org/content/302/2/759.abstract
AB The objective of the present study was to characterize a recently described binding site in the habenula, which has high affinity for [3H]epibatidine and low affinity for nicotine and acetylcholine. We report that the extension of this binding area in coronal and horizontal sections corresponds to the anatomical extension of the medial habenula. The affinity (KD) of the medial habenula receptors for [3H]epibatidine was estimated to be 0.5 nM using an autoradiographic saturation assay, whereas the affinity of the binding site for nicotine and acetylcholine was estimated to be 5 and 8 μM, respectively. The receptor density (Bmax) in the medial habenula was estimated to be about 1100 fmol/mg wet weight using [3H]epibatidine. The subunit composition of the “epibatidine receptor” was investigated by the ability of different compounds with affinity to various subtypes of nicotinic receptors to displace [3H]epibatidine bound to the receptor. The results suggest that the receptor contains α3 subunits but that it is unlikely to be an α3β4 nicotinic receptor. Systemic administration of epibatidine has analgesic effects in rats. Here we report that 2 × 1 μl of 10 nM epibatidine, resulting in a 2 × 10-fmol dose, administered directly to the medial habenula by bilateral stereotactic injection had an analgesic effect measured in the hot-plate test. This dose of epibatidine increased hot-plate latency significantly, whereas 2 × 2 fmol of epibatidine or 2 × 10 fmol of nicotine were without effect. This leads us to suggest that the medial habenular epibatidine binding site might be a valuable target for the development of non-opiate analgesics. The American Society for Pharmacology and Experimental Therapeutics