Immunodensity and mRNA expression of A<Subscript>2A</Subscript> adenosine,D<Subscript>2</Subscript> dopamine,and CB<Subscript>1</Subscript> cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: effect of antipsychotic treatment

Rationale  

Dopamine D₂ receptors are the main target of antipsychotic drugs. In the brain, D₂ receptors coexpress with adenosine A_2A and CB₁ cannabinoid receptors, leading to functional interactions.     

Pharmacokinetic-Pharmacodynamic Modeling of the Inhibitory Effects of Naproxen on the Time-Courses of Inflammatory Pain,Fever, and the <Emphasis Type="Italic">Ex Vivo</Emphasis> Synthesis of TXB<Subscript>2</Subscript> and PGE<Subscript>2</Subscript> in Rats

Purpose  

To quantify and compare the time-course and potency of the analgesic and antipyretic effects of naproxen in conjunction with the inhibition of PGE₂ and TXB₂.     

Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>-PEI-RITC Magnetic Nanoparticles with Imaging and Gene Transfer Capability: Development of a Tool for Neural Cell Transplantation Therapies

Purpose  

To develop Fe₃O₄-PEI-RITC magnetic nanoparticles with multimodal MRI-fluorescence imaging and transfection capability, for use in neural cell replacement therapies.     

Folate-PEG-CKK<Subscript>2</Subscript>-DTPA,A Potential Carrier for Lymph-Metastasized Tumor Targeting

Purpose  

A novel conjugate, Folate-PEG-CKK₂-DTPA, was designed and prepared as a carrier for lymphatic metastasized tumor imaging diagnosis and targeting therapy.     

In vivo electrophysiological and neurochemical effects of the selective 5-HT<Subscript>1A</Subscript> receptor agonist,F13640, at pre- and postsynaptic 5-HT<Subscript>1A</Subscript> receptors in the rat

Rationale  

F13640 (befiradol) is a novel 5-HT_1A receptor agonist with exceptional selectivity vs. other receptors and binding sites. It shows analgesic activity in animal models and is currently developed for human use.     

Comparative pharmacology of antipsychotics possessing combined dopamine D<Subscript>2</Subscript> and serotonin 5-HT<Subscript>1A</Subscript> receptor properties

Rationale  

There is increasing interest in antipsychotics intended to manage positive symptoms via D₂ receptor blockade and improve negative symptoms and cognitive deficits via 5-HT_1A activation. Such a strategy reduces side-effects such as the extrapyramidal syndrome (EPS), weight gain, and autonomic disturbance liability.     

Behavioral economics of food reinforcement and the effects of prefeeding,extinction, and eticlopride in dopamine D<Subscript>2</Subscript> receptor mutant mice

Rationale  

Several studies have investigated the reinforcing effects of food in genetically engineered mice lacking dopamine D₂ receptors (DA D₂Rs); however, behavioral economic analyses quantifying reinforcement have not been conducted.     

Genistein,a potent inhibitor of secretory phospholipase A<Subscript>2</Subscript>: a new insight in down regulation of inflammation

Objectives  

Some of the legumes, spices and medicinal herbs rich in genistein are known for their anti-inflammatory properties. Anti-inflammatory property of these herbs is determined by subjecting secretory phospholipase A₂ (sPLA₂) inhibition, a key enzyme in the inflammatory reactions by genistein.     

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A<Subscript>2A</Subscript> and A<Subscript>1</Subscript> antagonists

Rationale  

Adenosine A_2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone.     

The effects of PRX-07034, a novel 5-HT<Subscript>6</Subscript> antagonist,on cognitive flexibility and working memory in rats

Rationale  

Accumulating evidence indicates that schizophrenia and autism spectrum disorder patients are marked by cognitive deficits in working memory and strategy switching. There is accumulating evidence that 5-hydroxytryptamine (5-HT)₆ receptors may serve as a useful target to improve cognitive functioning.     

Effects of A<Subscript>2A</Subscript> adenosine receptor blockade or stimulation on alcohol intake in alcohol-preferring rats

Rationale  

A_2A adenosine receptors (A_2AARs) have been proposed to be involved in drug addiction; however, preclinical studies about the effects of A_2AAR ligands on alcohol consumption have provided inconsistent results.     

Increased cocaine self-administration in M<Subscript>4</Subscript> muscarinic acetylcholine receptor knockout mice

Rationale  

The reinforcing effects of cocaine are mediated by the mesolimbic dopamine system. Behavioral and neurochemical studies have shown that the cholinergic muscarinic M₄ receptor subtype plays an important role in regulation of dopaminergic neurotransmission.     

GABA<Subscript>B</Subscript> receptor blockade in the hippocampus affects sensory and sensorimotor gating in Long-Evans rats

Rationale  

Sensory and sensorimotor gating deficits are observed in schizophrenia. GABA_B receptor deficiency is also detected in the hippocampus of schizophrenic patients.     

Fast Surface Crystallization of Amorphous Griseofulvin Below <Emphasis Type="Italic">T</Emphasis><Subscript>g</Subscript>

Purpose  

To study crystal growth rates of amorphous griseofulvin (GSF) below its glass transition temperature (T _g) and the effect of surface crystallization on the overall crystallization kinetics of amorphous GSF.     

Interactive effects of mGlu5 and 5-HT<Subscript>2A</Subscript> receptors on locomotor activity in mice

Rationale  

Metabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)_2A activation, the interactions between serotonin 5-HT_2A receptors and mGlu receptors may prove to be important for our understanding of these diseases.     

CB<Subscript>1</Subscript> receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action

Rationale  

Cannabinoids have recently been identified as potential neuronal modulators of pruritic response, representing a potential target in the treatment of itch associated with a variety of pathophysiologic conditions. While the selective CB₁ receptor antagonist rimonabant is an established pruritic agent in both animal and clinical testing, its receptor mechanism of action and anatomical loci remain unclear.     

Pharmacological and behavioral characterization of the 5-HT<Subscript>2A</Subscript> receptor in C57BL/6N mice

Rationale  

The serotonin (5-HT) 2A receptor is implicated in numerous psychiatric disorders, making it an important, clinically relevant target. Despite the availability of transgenic mouse lines, the native mouse 5-HT_2A receptor is not well-characterized.     

The role of 5-HT<Subscript>1A</Subscript> receptors in phencyclidine (PCP)-induced novel object recognition (NOR) deficit in rats

Rationale  

Atypical antipsychotic drugs (APDs), many of which are direct or indirect serotonin (5-HT)_1A agonists, and tandospirone, a 5-HT_1A partial agonist, have been reported to improve cognition in schizophrenia.     

Synthesis, 5-HT<Subscript>1A</Subscript> and 5-HT<Subscript>2A</Subscript> receptor affinity and QSAR study of 1-benzhydryl-piperazine derivatives with xanthine moiety at N4

Abstract  

Three novel 1-benzhydryl-piperazines with xanthine moiety at N4 were synthesized and tested for 5-HT_1A and 5-HT_2A receptor affinity. One of the compounds showed the highest affinity (58.6 nM) and selectivity (34 times) to 5-HT_2A receptor known for this class of compounds. A set of the three new and 31 previously synthesized 1-arylpiperazines with xanthine moiety at N4 was compiled and a QSAR study was performed in order to rationalize the further synthesis. It was found that the 5-HT_1A affinity depends on the shape of the molecules (ovality and number of circuits), the distribution of the electron density in the structures (partial charges at piperazine N1 and xanthine N1) and their charge transfer ability (HOMO energy). The 5-HT_2A affinity depends on the lipophilicity of the ligands and the distribution of the electron density in the structures (partial charges at piperazine N4 and xanthine O6). The QSAR results are in a good agreement with known pharmacophore models.     

Repeated administration of the GABA<Subscript>B</Subscript> receptor positive modulator BHF177 decreased nicotine self-administration,and acute administration decreased cue-induced reinstatement of nicotine seeking in rats

Rationale  

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA_B receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA_B receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA_B receptor agonists, GABA_B receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists.