Metaphit-induced audiogenic seizures in mice: II. Studies on N-methyl-D-aspartic acid, GABA, and sodium channel receptors and on the disposition of metaphit in the brain.

We previously demonstrated that metaphit (a phencyclidine analogue with an acylating isothiocyanate group) induces occurrence of audiogenic seizures in mice exposed to audio stimulation 24 h after metaphit administration. We have studied various receptor systems associated with excitatory and inhibitory networks: sites for competitive and noncompetitive antagonists of the N-methyl D-aspartic acid (NMDA) receptor complex, for [3H]muscimol on the gamma-aminobutyric acid (GABA) receptor complex, and for [3H]batrachotoxinin A20-alpha-benzoate on the voltage-dependent sodium channel. Mice were examined for neurochemical changes at 24 h after pretreatment with metaphit, when susceptibility to audiogenic seizures is greatest.

Radiolabeling of dopamine uptake sites in mouse striatum: comparison of binding sites for cocaine, mazindol, and GBR 12935.

This study addressed the possibility of a unique binding interaction between cocaine and the dopamine transporter as compared with other blockers of dopamine uptake. Cocaine binding sites in a fresh P2 fraction of mouse striatum were labeled with [3H]CFT, a phenyltropane analog of cocaine also known as WIN 35,428, and compared with sites labeled with [3H]mazindol or [3H]GBR 12935. Under the conditions used, homogeneous binding was observed that was inhibited monophasically by cocaine, CFT, and mazindol; the same potencies were observed with the three radioligands.

Cocaine binding sites in mouse striatum, dopamine autoreceptors, and cocaine-induced locomotion.

BALB/cByJ mice received cocaine (25 mg/kg IP) once a day for 3 days, resulting in a greater locomotor response to cocaine on day 3 than on day 1. On day 4, a dose (0.03 mg/kg SC) of apomorphine, targeted at dopamine autoreceptors, caused the same degree of locomotor depression in cocaine- as in saline-pretreated mice.