Neuropharmacology
July 2013
Clinton E. Canal, Raymond G Booth, Drake Morgan
There are seemingly conflicting data in the literature regarding the role of serotonin (5-HT) 5-HT2C receptors in the mouse head-twitch response (HTR) elicited by the hallucinogenic 5-HT2A/2B/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Namely, both 5-HT2C receptor agonists and antagonists, regarding 5-HT2C receptor-mediated Gq-phospholipase C (PLC) signaling, reportedly attenuate...
Neuropharmacology
March 2012
Lucinda J Steward, Matthew D Kennedy, Brian J Morris et al.
Many antipsychotics (APDs) have a high affinity for muscarinic receptors, which is thought to contribute to their therapeutic efficacy, or side effect profile. In order to define how muscarinic receptor gene expression is affected by atypical or typical APDs, rats were treated with chronic (2.58 mg/kg) PCP (a psychotomimetic) or vehicle, plus clozapine (20 mg/kg/day) or haloperidol (1...
Neuropharmacology
March 2012
John D Elsworth, Stephanie M Groman, J David Jentsch et al.
Repeated, intermittent administration of the psychotropic NMDA antagonist phencyclidine (PCP) to laboratory animals causes impairment in cognitive and executive functions, modeling important sequelae of schizophrenia; these effects are thought to be due to a dysregulation of neurotransmission within the prefrontal cortex. Atypical antipsychotic drugs have been reported to have measurable, if...
Neuropharmacology
March 2012
Joshua S Rodefer, Samantha K Saland, Samuel J Eckrich
A number of selective phosphodiesterase (PDE) inhibitors have been demonstrated to improve learning in several rodent models of cognition. Given that schizophrenia is associated with impairments in frontal lobe-dependent cognitive functions (e.g., working memory and cognitive flexibility), we examined whether PDE inhibitors would attenuate cognitive deficits associated with schizophrenia....
Neuropharmacology
March 2012
Sam A Barnes, Jared W Young, Jo C Neill
It is well documented that schizophrenia patients exhibit dysfunction in various cognitive domains, including attention/vigilance, as demonstrated by impaired performance in the myriad of Continuous Performance Tests (CPTs). NMDA receptor antagonists provide a pharmacological model in animals of the cognitive disruption presented in the disorder. We therefore examined the effects of a...
Neuropharmacology
February 2012
Robert E Vann, D M Walentiny, J J Burston et al.
Marijuana's effects in humans are most often reported as intoxicating or therapeutic; yet, some humans report dysphoria or other negative affect. To evaluate whether differences in endocannabinoid levels might account for this variability, the present study examined whether sensitivity to cannabinoids changed when anandamide (AEA) metabolism was inhibited through administration of phenylmethyl...
Neuropharmacology
January 2012
Jesse S O Lindholm, Henri Autio, Liisa Vesa et al.
Accumulating evidence suggests that biogenic amine-based antidepressants act, at least in part, via regulation of brain-derived neurotrophic factor (BDNF) signaling. Biogenic amine-based antidepressants increase BDNF synthesis and activate its signaling pathway through TrkB receptors. Moreover, the antidepressant-like effects of these molecules are abolished in BDNF deficient mice....
Neuropharmacology
January 2012
Ronald S. Duman, Nanxin Li, Rong-Jian Liu et al.
Currently available medications have significant limitations, most notably low response rate and time lag for treatment response. Recent clinical studies have demonstrated that ketamine, an NMDA receptor antagonist produces a rapid antidepressant response (within hours) and is effective in treatment resistant depressed patients. Molecular and cellular studies in rodent models demonstrate that...
Neuropharmacology
December 2011
Erica Y Shen, Syed F. Ali, Jerrold S. Meyer
Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in...
Neuropharmacology
March 17, 2011
Carla M Nappi, Sean P A Drummond, Joshua M H Hall
Emerging evidence supports the notion of disrupted sleep as a core component of Posttraumatic Stress Disorder (PTSD). Effective treatments for nighttime PTSD symptoms are critical because sleep disruption may be mechanistically linked to development and maintenance of PTSD and is associated with significant distress, functional impairment, and poor health. This review aimed to describe the...
Neuropharmacology
February 23, 2011
Danuta Marona‐lewicka, Charles D. Nichols, David E Nichols
Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as "clearly a paranoid state." We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT(2A) receptors (LSD30), and the later temporal...
Neuropharmacology
January 20, 2011
Adam L. Halberstadt, Mark A. Geyer
Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in...
Neuropharmacology
2011
Maarten Van den Buuse, Emma Ruimschotel, Sally Martin et al.
37 citations
Serotonin-1A (5-HT(1A)) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT(1A) receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT(1A) receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of...
Neuropharmacology
2011
Robert W Gould, H Donald Gage, Matthew L Banks et al.
Cocaine self-administration alters brain dopaminergic and serotonergic function primarily in mesolimbic and prefrontal brain regions whereas 3,4-methylenedioxymethamphetamine (MDMA) self-administration predominately alters brain serotonergic function in a more widespread distribution across cortical regions. We previously reported that, compared to drug-naïve rhesus monkeys, self-administration...
Neuropharmacology
2011
Laura Hondebrink, Jan Meulenbelt, Marieke Meijer et al.
The popular synthetic drug of abuse 3,4-methylenedioxymethampetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) act mainly on the serotonergic system, though they also increase the amount of extracellular dopamine (DA) in the brain, presumably via reversal of the membrane dopamine transporter (DAT). As the involvement of exocytotic DA release is debated, we investigated if...
Neuropharmacology
2011
Natalia Realini, Daniela Vigano', Cinzia Guidali et al.
We have recently shown that chronic THC administration in adolescent female rats induces subtle but lasting alterations in the emotional circuit ending in depressive-like behaviour at adulthood. Here we describe other relevant depressive-like symptoms present in these animals. Adult female rats pretreated with THC display passive coping strategy towards acute stressful situations as...
Neuropharmacology
February 2010
Yan Xia, Cheng Z Wang, Jie Liu et al.
Phencyclidine is an N-methyl d-aspartate receptor (NMDAR) blocker that has been reported to induce neuronal apoptosis during development and schizophrenia-like behaviors in rats later in life. Brain-derived neurotrophic factor (BDNF) has been shown to prevent neuronal death caused by NMDAR blockade, but the precise mechanism is unknown. This study examined the role of the phosphatidylinositol-3...
Neuropharmacology
2010
Nora Laaris, Cameron H Good, Carl R. Lupica
Marijuana impairs learning and memory through actions of its psychoactive constituent, delta-9-tetrahydrocannabinol (Delta(9)-THC), in the hippocampus, through activation of cannabinoid CB1 receptors (CB1R). CB1Rs are found on glutamate and GABA neuron axon terminals in the hippocampus where they control neurotransmitter release. Previous studies suggest that Delta(9)-THC is a partial agonist...
Neuropharmacology
September 2009
Jacob M Hooker, Thomas A Munro, Cécile Béguin et al.
Salvinorin A (SA) is a potent kappa opioid agonist with a brief duration of action. Consistent with this, our previous positron emission tomography (PET) studies of carbon-11 labeled SA showed that brain levels decrease rapidly after intravenous administration. SA is rapidly metabolized, giving the much less potent salvinorin B (SB), which is presumed to be responsible in part for SA's brief...
Neuropharmacology
March 24, 2009
Activation of adenosine(1) (A(1)) receptors suppresses head shakes induced by a serotonergic hallucinogen in rats.
Neuropharmacology
2009
Massimo Grilli, Elisa Neri, Stefania Zappettini et al.
We investigated the effects of salvinorin A on the basal and the 12 mM K(+)-evoked release of preloaded [(3)H]noradenaline ([(3)H]NA) and [(3)H]serotonin ([(3)H]5-HT) from mouse hippocampal nerve terminals (synaptosomes), as well as on the basal and 12mM K(+)-evoked release of preloaded [(3)H]dopamine ([(3)H]DA) from mouse striatal and prefrontal cortex (PFc) synaptosomes. Salvinorin A...
Neuropharmacology
December 2008
Matthew R. Skelton, Jessica A Able, Curtis E. Grace et al.
3,4-Methlylenedioxymethamphetamine (MDMA) administration (4 x 15 mg/kg) on a single day has been shown to cause path integration deficits in rats. While most animal experiments focus on single binge-type models of MDMA use, many MDMA users take the drug on a recurring basis. The purpose of this study was to compare the effects of repeated single-day treatments with MDMA (4 x 15 mg/kg) once...
Neuropharmacology
October 2008
Jack W Lipton, Emeline G Tolod, Valerie B Thompson et al.
The current study examined whether modest concentrations of MDMA could increase the survival and/or neurite outgrowth of fetal midbrain dopamine (DA) neurons in vitro since increased DA neurite outgrowth has been previously observed in vivo from prenatal exposure. MDMA concentrations in fetal brain were quantified to determine relevant in vivo concentrations to employ in vitro. A dose response...
Neuropharmacology
July 19, 2008
Jason R. Clapper, Regina A. Mangieri, Daniele Piomelli
The endocannabinoid system modulates neurotransmission at inhibitory and excitatory synapses in brain regions relevant to the regulation of pain, emotion, motivation, and cognition. This signaling system is engaged by the active component of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC), which exerts its pharmacological effects by activation of G protein-coupled type-1 (CB1) and type-2 (CB2)...
Neuropharmacology
July 2, 2008
John A Allen, Prem N. Yadav, Bryan L. Roth
5-HT(2A) serotonin receptors are essential molecular targets for the actions of LSD-like hallucinogens and atypical antipsychotic drugs. 5-HT(2A) serotonin receptors also mediate a variety of physiological processes in peripheral and central nervous systems including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. Scaffolding proteins have emerged as...