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The aim of the present study is to test a hypothesis that 5-HT(1A) and 5-HT(2C) receptors in the amygdala play an important role in the regulation of anxiety behaviors. We examined alterations in anxiety-like behaviors after manipulation of the expression of 5-HT(1A) and 5-HT(2C) receptors in the amygdala using recombinant adenovirus approaches. Recombinant adenoviruses containing a 5-HT(1A) promoter-controlled 5-HT(1A) antisense sequence or a 5-HT(2C) promoter-controlled 5-HT(2C) sense sequence were injected into the amygdala. Elevated plus-maze (EPM) and open field tests were conducted to determine anxiety-like behavior and locomotor activity. Reductions in the expression of 5-HT(1A) receptors in the amygdala significantly attenuated the time spent in the open arms of EPM and time spent in the center of an open field. Reduction in the percent of time spent in the open arms of EPM is negatively correlated with the density of 5-HT(1A) receptors in the central amygdala. On the other hand, increased expression of 5-HT(2C) receptors reduced the time spent in the open arms of EPM and time spent in the center of an open field. The reductions in the time spent and distance traveled in the open arms of EPM were correlated to the density of 5-HT(2C) receptors in the basolateral nucleus of amygdala. These data suggest that amygdaloid 5-HT(1A) receptors produce anxiolytic and 5-HT(2C) receptors produce anxiogenic effects. Together, the present results demonstrate the important role of the amygdaloid 5-HT(1A) and 5-HT(2C) receptors in the regulation of anxiety-like behaviors. This article is part of a Special Issue entitled 'Anxiety and Depression'., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Serotonin 2A (5-HT2A) receptors are coupled to Galphaq and Galpha11 proteins to activate phospholipase C (PLC). Regulators of G-protein signaling proteins (RGS) modulate G-protein signaling by accelerating the intrinsic GTPase activity of Galphaq and Galpha11. This study investigated the effects of over-expression of wild-type Galphaq proteins (Gq-Tg) and over-expression of RGS-insensitive Galphaq proteins (G188S, RGSi-Tg) on 5-HT2A receptor mediated signaling in transgenic rats. Over-expression of wild-type Galphaq and RGS insensitive mutant Galphaq did not produce significant alterations in the levels of Galpha11, RGS2, RGS4, RGS7, RGS16 or 5-HT2A proteins. RGSi-Tg rats had higher oxytocin and corticosterone responses to (-)DOI, a 5-HT2A/2C receptor agonist, compared to Gq-Tg rats. RGSi-Tg and Gq-Tg rats had higher ACTH responses to (-)DOI compared to control rats. Similarly, 5-HT-stimulated PLC activity in the frontal cortex was higher in RGSi-Tg and Gq-Tg rats compared to control rats. In contrast, GTPgammaS-stimulated PLC activity was higher in Gq-Tg rats but not in RGSi-Tg rats compared to control rats. There was a small but statistically significant increase in the affinity of [125I]-DOI labeled 5-HT2A receptors in RGSi-Tg rats and Gq-Tg rats compared to controls. There were no significant differences in Bmax and Kd of [3H] ketanserin labeled 5-HT2A receptors among the three groups. These data suggest that the effect of RGS proteins on 5-HT2A receptor signaling is cell type specific. In transgenic rats over-expressing Galphaq, endogenous RGS proteins have a negative effect on 5-HT2A receptor-mediated oxytocin release. In contrast, endogenous RGS protein had no impact on 5-HT2A receptor-mediated ACTH release in transgenic rats.

Regional distribution of brain perfusion imaging agents, [131I]N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]1,3 propanediamine (HIPDM) and [131I]-N-isopropyl-p-iodoamphetamine (IMP), was compared with the distribution of patterns of [14C]L-methionine and [14C]D-glucose in normal and tumour bearing rat brains using autoradiographic technique. There was higher concentration of the radiopharmaceutical in grey than white matter in normal rat brain. Autoradiographs of brain tumour sections showed very low uptake of [131I]HIPDM and [131I]IMP as compared to normal brain tissue. There was moderate concentration of [14C]D-glucose and avid uptake of [14C]L-methionine in tumours. Autoradiographic study is useful for evaluating distribution patterns of radiopharmaceuticals.

Biodistribution of N-isopropyl-p-iodoamphetamine (IMP) was evaluated in mice. After synthesis of IMP and exchange labeling with radioactive iodine, IMP was injected intravenously in male ddY mice. Activity in the brain reached 8.0 (%dose/g), at 10 min after injection and it was almost constant till 120 min. Activities in the lung and heart were high just after injection, decreased rapidly and was almost constant from 30 to 120 min. Activity in the liver increased slowly compared with other organs, and reached peak level at 60 min. In autoradiography, almost the same activity in the spinal cord as the brain was observed. Uptake and excretion of IMP were shown in kidneys and stomach, which may be the main route of the excretion of IMP and their metabolites. We concluded IMP showed good uptake in the central nervous system.

Factor analysis of dynamic scintigraphic studies has been proposed for a variety of clinical applications. This method also called FADS (Factor Analysis of Dynamic Structures) enables spatial separation of complex images into discrete factors according to their time/activity characteristics. FADS, which does not require a priori formulation of a compartmental model of tracer kinetics, is particularly suitable for the evaluation of new radiolabeled compounds as potential radiopharmaceuticals. In animals as well as in humans it is possible to obtain information on the spatial time-distribution of tracers by analyzing computer acquired scintigraphic studies. On the basis of data obtained and analyzed with this method using [123I]IMP in humans, dogs, rabbits and rats, with two 99mTc labeled monoclonal antibodies in dogs and with 99mTc DTPA in renal transplants, we recommend this method as an adjunct in radiopharmaceutical development and evaluation.

Demethylation of psychotomimetic compounds was measured by labeling each methyl and methoxy substitutent separately with 14C and injecting it into rats, intravenously and intracerebrally. Expired [14C]CO2 was measured continuously and the resultant multi-exponential curves yielded rates and integral demethylation. 5-Methoxy-N,N-dimethyltryptamine was not demethylated, eliminating one proposed metabolic pathway. 2,4,5-Trimethoxyphenalkylamines were demethylated less in the brain than peripherally, markedly so at the p-methoxy position, suggesting a possible biochemical site for endogenous induction of psychosis.

The relation between brain uptake of radiolabeled n-isopropyl-p-iodoamphetamine [( 123I]IMP) and serotonin re-uptake sites was studied in vivo by lesioning serotonergic nerve endings. The reduction of brain serotonin demonstrated the effectiveness of the procedure. Accumulation of radioactivity/g brain tissue was higher in the lesioned than in the sham-operated rats. This was explained by the loss of body weight of the lesioned animals, allowing an increased distribution to the brain. These results demonstrate that the in vivo distribution and binding of [123I]IMP in the brain is not limited to the specific serotonin re-uptake sites on nerve endings.

Ruthenocene amphetamine analogues have the same brain uptake as iodo-labelled amphetamines. This paper compares the organ-distribution of 103Ru labelled ruthenocene- or ferrocene-amphetamine analogues in mice and rats with the same amphetamine in which H-atoms were partly substituted by D-atoms. The uptake in the brain is increased up to 180-200% for deuterium substituted compounds. The pattern of excreted metabolites leads to the conclusion that the deuterated amphetamines are more slowly metabolised than normal (H) compounds.