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OBJECTIVE The cellular substrate of hippocampal dysfunction in schizophrenia remains unknown. We tested the hypothesis that hippocampal interneurons are abnormal in schizophrenia, but that the total number of hippocampal neurons in the pyramidal cell layer is normal. METHODS We collected whole hippocampal specimens of 13 subjects with schizophrenia and 20(More)
Lysergic acid diethylamide (LSD) produces altered mood and hallucinations in humans and binds with high affinity to serotonin-2A (5-HT(2A)) receptors. Although LSD interacts with other receptors, the activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic properties of LSD. The goal of this study was to identify the brain sites activated(More)
The mammalian target of rapamycin (mTOR) complex 2 (mTORC2) is a multimeric signaling unit that phosphorylates protein kinase B/Akt following hormonal and growth factor stimulation. Defective Akt phosphorylation at the mTORC2-catalyzed Ser473 site has been linked to schizophrenia. While human imaging and animal studies implicate a fundamental role for Akt(More)
Serotonin [i.e., 5-hydroxytryptamine (5-HT)]-targeted antidepressants are in wide use for the treatment of mood disorders, although many patients do not show a response or experience unpleasant side effects. Psychostimulants, such as cocaine and 3,4-methylenedioxymethamphetamine (i.e., "ecstasy"), also impact 5-HT signaling. To help dissect the contribution(More)
RATIONALE Hallucinogenic serotonin 2A (5-HT(2A)) receptor partial agonists, such as (+ or -)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), induce a frontal cortex-dependent head-twitch response (HTR) in rodents, a behavioral proxy of a hallucinogenic response that is blocked by 5-HT(2A) receptor antagonists. In addition to 5-HT(2A)(More)
Activation of 5-hydroxytryptamine2C (5-HT(2C)) receptors by the 5-HT(2) receptor agonist m-chlorophenylpiperazine (m-CPP) elicits anxiety in humans and anxiety-like behavior in animals. We compared the effects of m-CPP with the anxiogenic GABA(A) receptor inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) on both anxiety-like behavior and(More)
The serotonergic system regulates a wide range of behavior, including mood and impulsivity, and its dysregulation has been associated with mood disorders, autism spectrum disorder, and addiction. Diabetes is a risk factor for these conditions. Insulin resistance in the brain is specifically associated with susceptibility to psychostimulant abuse. Here, we(More)
Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of(More)
CONTEXT Postmortem studies have reported decreased density and decreased gene expression of hippocampal interneurons in bipolar disorder, but neuroimaging studies of hippocampal volume and function have been inconclusive. OBJECTIVE To assess hippocampal volume, neuron number, and interneurons in the same specimens of subjects with bipolar disorder and(More)
It has been hypothesized that dopamine(D1) and serotonin(2) receptors become sensitized to agonist-mediated regulation of gene expression following loss of dopaminergic innervation to the striatum. We have previously demonstrated that the combined administration of dopamine(D1) and serotonin(2) receptor agonists to dopamine-depleted adult rats induced(More)