Neuropeptide Y (NPY) potently inhibits excitatory synaptic transmission in the hippocampus, acting predominantly via a presynaptic Y(2) receptor. Recent reports that the Y(5) receptor may mediate the anticonvulsant actions of NPY in vivo prompted us to test the hypothesis that Y(5) receptors inhibit synaptic excitation in the hippocampal slice and, furthermore, that they are effective in an in ...

We have studied the effect of guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), a non-hydrolyzable analogue of GTP, on agonist and antagonist binding to bovine hippocampal 5-hydroxytryptamine (5-HT)(1A) receptor in native membranes. Our results show that the specific binding of the agonist is inhibited with increasing concentrations of GTP-gamma-S along with a reduction in binding affinity. In...

BACKGROUND We have recently reported that serotonin(4) (5-HT(4)) receptor agonists have a promising potential as fast-acting antidepressants. Here, we assess the extent to which this property may be optimized by the concomitant use of conventional antidepressants. METHODOLOGY/PRINCIPAL FINDINGS We found that, in acute conditions, the 5-HT(4) agonist prucalopride was able to counteract the inh...

Transcripts encoding 5-HT(2C) receptors are modified posttranscriptionally by RNA editing, generating up to 24 protein isoforms. In recombinant cells, the fully edited isoform, 5-HT(2C-VGV), exhibits blunted G-protein coupling and reduced constitutive activity. The present studies examine the signal transduction properties of 5-HT(2C-VGV) receptors in brain to determine the in vivo consequences...

Roxindole, a DA D2 receptor agonist (2-16 mg/kg) produced dose-dependent increase in percentage antinociception. The effect which was blocked by DA D2 antagonist (-)sulpiride (50 mg/kg) and 5-HT1A receptor antagonist (-) pindolol (5 mg/kg). Roxindole (4 and 8 mg/kg) reversed both naloxone (20 mg/kg)-induced hyperalgesia and reserpine (2 mg/kg)-induced hyperalgesia. This reversal was sensitive t...

A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at serotoni...

Paradoxical behavioral responses to nonselective neuropsychiatric drugs are frequently encountered and poorly understood. We report that a single receptor gene mutation produces a paradoxical response to the nonspecific serotonin receptor agonist m-chlorophenylpiperazine (mCPP). Although this compound normally suppresses locomotion, it produces hyperactivity in mice bearing a targeted mutation ...

1 The beta-adrenoceptor agonist isoprenaline normally causes only a small and inconsistent increase in the membrane potential of cells in guinea-pig liver slices, in contrast to the large hyperpolarizations seen with alpha-agonists. However, after a selective alpha-adrenoceptor agonist has been applied, the response to isoprenaline becomes greatly enhanced. 2 Simultaneous application of small d...

Ligand-gated ion channels participate in synaptic transmission, and they are involved in neurotransmitter release. The functions of the channels are regulated by a variety of modulators. The interaction of 2,2,2-trichloroethanol, the active hypnotic metabolite of chloral hydrate, with the 5-hydroxytryptamine (5-HT) (serotonin) type 3 receptor results in a positive allosteric modulation. We have...