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Previous studies have demonstrated that antagonists at the NMDA receptor are as efficacious as tricyclic antidepressants in pre-clinical antidepressant screening procedures and in blocking or reversing the behavioral deficits associated with animal analogs of major depressive symptomatology. The NMDA receptor complex gates Ca2+, which interacts with(More)
A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some(More)
Local anesthetics bind to dopamine transporters and inhibit dopamine uptake in rodent brain. Additionally, local anesthetics are self-administered in rhesus monkeys. The present study determined binding affinities of cocaine and five local anesthetics at dopamine transporters in rhesus monkey brain, and compared binding affinities to published(More)
The past decade has seen a steady accumulation of evidence supporting a role for the excitatory amino acid (EAA) neurotransmitter, glutamate, and its receptors in depression and antidepressant activity. To date, evidence has emerged indicating that N-methyl-d-aspartate (NMDA) receptor antagonists, group I metabotropic glutamate receptor (mGluR1 and mGluR5)(More)
Chronic antidepressant treatment results in adaptation of the NMDA receptor complex in the rodent cortex. This adaptation consists of a reduction in the potency of glycine to displace [3H]5,7-dichlorokynurenic acid from strychnine-insensitive glycine receptors and a reduction in high affinity, glycine-displaceable [3H]CGP-39653 binding to glutamate(More)
Neonatal exposure to antidepressants, including selective serotonin reuptake inhibitors such as citalopram, induces behavioral disturbances which persist in mature rats. These disturbances have been proposed to model the symptoms of endogenous depression. However, to date there is scant evidence for the predictive validity of any of these behaviors in(More)
Neonatal (postnatal days 8-21) exposure of rats to the selective serotonin reuptake inhibitor (SSRI), citalopram, results in persistent changes in behavior including decreased sexual activity in adult animals. We hypothesized that this effect was a consequence of abnormal stimulation of 5-HT(1A) and/or 5-HT(1B) receptors as a result of increased synaptic(More)
Behavioral and neurochemical effects of haloperidol (D2-dopamine antagonist) and SCH-23390 (D1-dopamine antagonist) were examined in unlesioned rats and in rats lesioned with 6-hydroxy-dopamine (6-OHDA) as adults or as neonates. In unlesioned rats, chronic haloperidol treatment (15 days) resulted in an increase in D2-dopamine receptor density, as measured(More)
NMDA antagonists mimic the effects of clinically effective antidepressants in both preclinical tests predictive of antidepressant action and procedures designed to model aspects of depressive symptomatology. These findings led to experiments demonstrating that chronic administration of NMDA antagonists to rodents results in a downregulation of cortical(More)
Rationale: Drugs that are self-administered appear to vary in their potency and effectiveness as positive reinforcers. Understanding mechanisms that determine relative effectiveness of drugs as reinforcers will enhance our understanding of drug abuse. Objectives: The hypothesis of the present study was that differences among dopamine transporter (DAT)(More)