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

Abstract

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)

Cataleptic effects of γ-hydroxybutyrate (GHB) and baclofen in mice: mediation by GABAB receptors, but differential enhancement by N-methyl-d-aspartate (NMDA) receptor antagonists

“…The doses at which the NMDA antagonists enhanced GHB-induced catalepsy were 4-to 16-fold lower than those reported to block NMDA-induced convulsions ( Fig. 2a) and were very similar to those reported (Maurice and Vignon 1990) to inhibit TCP-binding in vivo (Fig. 2b).…”

“…The main finding of this study is that GHB-induced catalepsy was selectively enhanced by dizocilpine, PCP, and ketamine, with a potency order (i.e., dizocilpine > PCP > ketamine, based on their minimum effective dose: 0.178, 3.2, and 17.8 mg/kg, respectively) similar to their relative potencies to antagonize effects of NMDA in vivo (e.g., ) and consistent with their relative affinities at binding sites in the ion channel of the NMDA receptor complex labeled with PCP (e.g., Wong et al 1988) or the PCP derivative, TCP (e.g., Maurice and Vignon 1990). Dizocilpine significantly increased catalepsy when given alone.…”

“…Further studies examining the different GABA B mechanisms underlying effects of GHB and baclofen may help to explain why GHB is effective to treat narcolepsy and is abused, whereas there is no evidence that baclofen is effective in any sleep disorder and no evidence that baclofen is abused. Relation between the potencies of the NMDA antagonists ketamine, phencyclidine (PCP), and dizocilpine (MK-801) to enhance GHB-induced catalepsy in mice and their potencies to a antagonize NMDA-induced convulsions in mice , b inhibit in vivo labeling of the NMDA receptor-associated ion channel with the phencyclidine derivative [ 3 H]TCP in mouse brain, which correlates strongly (r=0.93) with in vitro [ 3 H]TCP binding in rat brain (Maurice and Vignon 1990), c inhibit [ 3 H]dopamine uptake into rat striatal synaptosomes (Johnson and Snell 1985;Snell et al 1988), and d inhibit [ 3 H]MPP + uptake by rat organic cation transporter 1 (OCT1) in transfected HEK293 cells (Amphoux et al 2006). MSD minimum significant dose, r Pearson's correlation coefficient…”

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

“…While the link between altered sensorimotor gating and glutamate is relatively well established, that between Oxt and glutamate is more speculative. The widespread distribution of the Oxt [57][58][59] and NMDA receptors 60,61 in the mouse, including within the CSPP circuitry, certainly affords many opportunities for interactions. Most research to date examining interactions between the Oxt and glutamatergic systems has focused on the hypothalamic magnocellular Oxt neurons where glutamatergic circuits synchronize the bursting activity of magnocellular Oxt neurons in organotypic cultures 62 and glutamate is responsible for the fast excitatory input into the magnocellular neurons.…”

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

“…On one hand, its ID 50 is 6.3 mg/kg s.c. for the striatal DAT, labeled in vivo using [ 3 H]BTCP (Maurice et al 1991). On the other hand, BTCP fails to significantly inhibit the in vivo binding of [ 3 H]TCP to the PCP site in the mouse hippocampus, cortex and cerebellum, at 50 mg/kg (Maurice and Vignon 1990) and the in vivo binding of [ 3 H]SKF-10,047 to the sigma 1 site in the mouse hippocampus, at 60 mg/ kg (T. Maurice, unpublished result). BTCP thus appears suitable as a highly selective indirect dopaminergic agonist for comparison with cocaine.…”