Ontogeny of the N-methyl-D-aspartate (NMDA) receptor system and susceptibility to neurotoxicity.

The NMDA receptor has been widely investigated in recent years as a target for the pharmacological management of seizures, pain and a variety of neurological disorders. Its role in normal central nervous system (CNS) activity and development, as well as in the development of CNS abnormalities and neurodegeneration has also been of interest. The NMDA receptor is one of three pharmacologically distinct subtypes of ionotropic receptor channels that are sensitive to the endogenous excitatory amino acid, L-glutamate.

Modulation of intravenous cocaine effects by chronic oral cocaine in humans.

Rationale: Agonist therapies have proven effective for the treatment of substance dependence disorders; limited data is available on their feasibility for treating cocaine dependence.

Objectives: This laboratory study was designed to test the safety and utility of employing an agonist substitution therapy for the treatment of cocaine dependence in humans.

Methods: Oral cocaine served as the agonist treatment and was administered chronically over a range of doses to volunteers with cocaine abuse histories (n=8).

Human pharmacology of the opioid neuropeptide dynorphin A(1-13).

We evaluated the human pharmacology of dynorphin A(1-13) and determined whether this peptide can modulate naloxone-precipitated withdrawal effects. Such information could help determine its receptor mechanism of action and whether dynorphin is useful for treating opioid dependence. Six opioid-experienced subjects participated in a within-subject, placebo-controlled design.

Absence of acute cocaine interactions with the MAO-B inhibitor selegiline.

Selegiline, an irreversible monoamine oxidase-B (MAO-B) inhibitor, is under investigation as a treatment for cocaine relapse prevention. To evaluate its safety, human volunteers (n = 5) received intravenous cocaine (0, 20 and 40 mg, 1 h apart) following treatment with placebo or selegiline (10 mg, p.o.

Acute interactive effects of MK-801 and morphine on cortical EEG and EEG power spectra in rats.

The interaction between MK-801 and morphine-induced effects on cortical electroencephalography (EEG) was investigated. Rats were administered one of five MK-801 doses (IP) prior to morphine (IV). MK-801 dose-dependently increased morphine-induced global spectral power, duration of morphine-induced EEG bursts and latency to sleep onset, and decreased morphine-induced mean frequency, mobility, complexity, and edge frequency.

Interactive effects of MK-801 and morphine on EEG, EEG power spectra and behavior in rats: II. Morphine dependence.

A potential interaction between MK-801 and the cortical electroencephalographic (EEG) and behavioral expressions of morphine dependence in female Sprague-Dawley rats was assessed. Rats were treated chronically (7 days) with either morphine alone, morphine and MK-801, MK-801 alone or saline vehicle alone. On day 8 all rats received morphine alone followed by naloxone.

Interactive effects of MK-801 and morphine on EEG, EEG power spectra and behavior in rats: I. Morphine tolerance development.

This study investigated a potential interaction between MK-801 and morphine tolerance using electroencephalography (EEG), EEG spectral parameters and behavior in the rat. Rats were treated for 7 days with morphine alone or with morphine and MK-801. Control groups received chronic MK-801 alone or saline.

Potentiation of quinolinate-induced hippocampal lesions by inhibition of NO synthesis.

Low doses of quinolinic acid (QUIN) administered intracerebroventricularly (ICV) to rats produced either no damage or mild to moderate damage in the pyramidal cell layer of the hippocampus and resulted in mild, limbic seizures in the majority of animals treated. The same dose of QUIN following ICV pretreatment with the nitric oxide synthase inhibitor N-nitro-L-arginine (NARG), produced extensive hippocampal lesions with complete loss of the pyramidal layer in 50% of the animals, and moderate damage with total neuronal loss in areas CA1 and CA3 in the remainder of the group. Animals treated with both NARG and QUIN also exhibited a greater incidence of severe convulsive behavior (9/11) and 3 deaths.