In vivo labelling of the mouse dopamine uptake complex with the phencyclidine derivative [3H]BTCP.
[3H]BTCP ([3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine), a phencyclidine (PCP) derivative which binds with a high affinity to the dopamine (DA) uptake complex in vitro, has been tested for in vivo binding to mouse brain. Using [3H]BTCP as a tracer (5 microCi, i.v.) we found the striatum as the region which accumulated the largest amount of radioactivity (58 dpm/mg tissue). In other brain regions the radioactive level (about 20 dpm/mg tissue) was close to the non-specific binding determined by an injection of unlabeled BTCP (40 mg/kg, s.c.) 2 h prior to the [3H]BTCP injection. In the striatum [3H]BTCP binding was inhibited in a dose-dependent manner by unlabeled BTCP (ID50 = 6.34 mg/kg) and nomifensine (ID50 = 11.06 mg/kg). It was unaffected by the DA receptor antagonist haloperidol and by PCP or its analog TCP at doses of 10 mg/kg. These results suggest that [3H]BTCP binds to the dopamine uptake complex in the mouse brain in vivo. Thus, although PCP has no effect on [3H]BTCP binding in these experimental conditions, this in vivo binding model will be useful for the determination of the precise interaction of PCP and its derivatives with the striatal dopamine uptake complex in vivo independently of their interaction with the N-methyl-D-aspartate receptor-channel complex.
INSERM U 249, Ecole Nationale Supérieure de Chimie, Montpellier, France.
T
T
Maurice
J
J
Vignon
J M
JM
Kamenka
R
R
Chicheportiche
D000818:Animals; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry; D003342:Corpus Striatum / Q000737:chemistry; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009830:Olfactory Bulb / Q000737:chemistry; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D010622:Phencyclidine; D004298:Dopamine