Biomedical subjects

T Maurice

Publications and source records attributed to T Maurice.

44 records · Page 3Linked to original sources

PubMed1993

Endogenous dopamine differently affects N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine and cocaine binding to the dopamine uptake complex.

1. [3H]N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP) labels in vivo the dopamine uptake complex in the mouse striatum. 2. In mice treated with gamma-butyrolactone (GBL, 400 mg/kg), [3H]BTCP specific binding was increased and ID50 values of BTCP and cocaine for the prevention of [3H]BTCP binding were significantly lowered. 3. In GBL-treated mice, cocaine (5 mg/kg, s.c.) had no effect on the BTCP ID50 value, whereas GBR 12783 (2 mg/kg, s.c.) increased it significantly. 4. Thus in vivo, endogenous dopamine and cocaine are competitive and non-competitive inhibitors, respectively, of the binding of [3H]BTCP.

4-Butyrolactone↗

PubMed1992

Regional differences in the effect of N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) on extracellular dopamine levels: an in vivo microdialysis study.

N-[1-(2-Benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) is a phencyclidine derivative highly selective for the dopamine (DA) uptake complex. Its effect on extracellular DA levels was studied by in vivo microdialysis on freely moving rats. In the striatum, BTCP induced a dose-dependent increase in DA levels, without affecting DA metabolites. In the nucleus accumbens, a lower increase in DA was observed, but with concomitant decreases in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). These experiments show that the effects of BTCP on extracellular DA levels are significantly different on extrapyramidal and mesolimbic dopaminergic terminals.

Animals↗

PubMed1991

Desipramine and the phencyclidine derivative BTCP differently inhibit [3H]TCP binding to high- and low-affinity sites.

The effects of N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and desipramine on [3H]N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding were investigated in vivo and in vitro. In the cerebrum, both drugs were competitive inhibitors of high-affinity [3H]TCP binding. Conversely, in the cerebellum, they were non-competitive inhibitors of low-affinity [3H]TCP binding. These results imply that the different [3H]TCP binding sites have distinct pharmacological properties, and show that, although chemically related to TCP, BTCP has an effect similar to that of desipramine.

Animals↗

PubMed1991

Modulation by dopamine of [3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP, a phencyclidine derivative) binding to the dopamine uptake complex.

The modulation by dopamine of the binding of [3H]BTCP to the dopamine (DA) uptake complex was investigated in vivo (in control, reserpine- and L-DOPA-treated mice) and in vitro (on membrane preparations of the striatum of the rat). In both cases increasing doses of DA exerted a non-competitive inhibition of binding of [3H]BTCP, with a Ki value close to its K0.5, determined in competition experiments. Amphetamine and cocaine were also non-competitive inhibitors of the binding of [3H]BTCP, while GBR 12783 was competitive. In the presence of DA, the amount of cocaine required to inhibit the binding of [3H]BTCP was increased both in vitro and in vivo. These results suggest that inhibitors of the uptake of DA, such as BTCP or GBR 12783, modulate allosterically the uptake of DA, by binding to a site different from the DA recognition site. Cocaine, however, seems to share the same recognition site as DA.

Animals↗

PubMed1991

Differential interaction of phencyclidine-like drugs with the dopamine uptake complex in vivo.

The phencyclidine (PCP) derivative, [3H]N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine ([3H]BTCP), was used to label in vivo the dopamine uptake complex in mouse brain. The striatum accumulated the highest level of total and specific binding. Drugs which bind to the dopamine uptake site inhibited [3H]BTCP binding on an order similar to their in vitro affinities for the high-affinity [3H]BTCP site. Drugs which label selectively other monoamine uptake complexes. PCP, or sigma recognition sites were ineffective at doses up to 40 mg/kg. PCP bound to and dissociated from the dopamine uptake complex very rapidly. N-[1-(2-Thienyl)cyclohexyl]pideridine (TCP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) had no effect at any time or at any dose. These results imply that the pharmacological effects of PCP are due to its simultaneous interaction with the dopamine uptake complex and the PCP receptor. Conversely, TCP and MK-801, which have the same behavioral properties as PCP, exert their action only through the interaction with the PCP receptor.

Animals↗

PubMed1990

In vivo labeling of phencyclidine (PCP) receptors with 3H-TCP in the mouse brain.

The phencyclidine (PCP) derivative N-[1-(2-thienyl)cyclohexyl]-piperidine (3H-TCP) was used to label in vivo the N-methyl-D-aspartate (NMDA) receptor-associated ionic channel in the mouse brain. After the injection of a tracer dose of 3H-TCP, a spread labeling throughout the brain was observed, but was the highest in the cerebellum. Preadministration of unlabeled TCP (30 mg/kg) resulted in a 90% reduction of 3H-TCP binding. PCP, TCP, MK-801, dexoxadrol, ketamine, and SKF 10,047 isomers dose-dependently prevented the in vivo 3H-TCP binding. ID50 determined in the cerebrum and the cerebellum were respectively correlated with K0.5 for 3H TCP high (rat cortex) and low affinity (rat cerebellum) sites in vitro. The pharmacological specificity of the 3H-TCP binding site in the cerebellum was significantly different from that in the cerebrum. ID50 values were generally higher than in the cerebrum and, particularly, MK-801, the most potent drug in the cerebrum, was without significant effect in the cerebellum, at any time and at doses as high as 30 mg/kg. N-[1-(2-benzo(b) thiophenyl)cyclohexyl]piperidine (BTCP), desipramine, and atropine showed a more efficient prevention of 3H-TCP binding in the cerebellum than in the cerebrum. The prevention of the binding by TCP or PCP, at doses close to their ID50 values, was rapid and then decreased slowly. The effect of MK-801 was long-lasting. This study confirm previous in vitro studies: 3H-TCP is an efficient tool for the labeling of the NMDA receptor-associated ionic channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

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.

Animals↗

PubMed1989

The [Ca2+]i increase induced in murine thymocytes by extracellular ATP does not involve ATP hydrolysis and is not related to phosphoinositide metabolism.

We have previously demonstrated that exogenous ATP can give medullary thymocytes the calcium message required for the induction of their blastogenesis. In the present study, using the highly sensitive calcium indicator Indo-1, we have measured the effect of exogenous nucleotides on the cytosolic-free calcium concentration [Ca2+]i of thymocytes, and determined inositol phosphate (IP) formation in the same cells, in parallel assays. The results were compared to those obtained with the mitogenic lectin concanavalin A (ConA) in similar experiments. They show that ATP does not mobilize calcium from its internal stores but stimulates its influx from the extracellular medium. Nevertheless, these data do not rule out the possibility that the nucleotide acts through specific P2 purinergic sites.

Adenosine Triphosphate↗