Oxotechnetium 99mTcO[SN(R)S][S] complexes as potential 5-HT1A receptor imaging agents.

A series of 99mTcO[SN(R)S][S] complexes carrying the 1-(2-methoxyphenyl)piperazine moiety on the tridentate ligand [SN(R)S] was synthesized. For structural characterization and for in vitro binding assays the analogous oxorhenium complexes were prepared. As demonstrated by appropriate competition binding tests in rat hippocampal preparations, all oxorhenium analogues showed affinity for the 5-HT(1A) receptor binding sites with IC(50) values at the nanomolar range (IC(50)= 5.8-103 nM). All 99mTcO[SN(R)S]/[S] complexes showed significant brain uptake in rats at 2 min p.i. (0.24-1.31% ID). However, a clear correlation between distribution of radioactivity in the brain and distribution of 5-HT(1A) receptors could not be established.

Differential alterations in basal and D-amphetamine-induced behavioural pattern following 6-OHDA or ibotenic acid lesions into the dorsal striatum.

It is well known that the corpus striatum is related to the sterotyped activation induced by several psychostimulants. In this study we analyzed the effects of 6-OHDA, in comparison with those of ibotenic acid lesions, into the dorsal striatum, on the behavioural pattern induced by saline or D-amphetamine treatment. A computerized technique for recording the animal motor activity was developed in order to define in a detailed way the behavioural profile in lesioned and sham-operated rats induced by the saline or D-amphetamine treatment. A 6-OHDA lesion into the dorsal striatum modified the basal behavioural pattern which was mainly characterized by reduced motor activation while ibotenic acid lesion affected the structure of the basal behavioral pattern. D-Amphetamine administration in 6-OHDA lesioned rats induced a behavioural stimulation, but a decreased motor and stereotyped activation was observed compared to the sham-operated animals treated with D-amphetamine. In contrast, D-amphetamine administration in the ibotenic acid-lesioned rats induced a motor and stereotyped activity which was not reduced compared to that seen after D-amphetamine treatment in sham-operated rats. These results suggest that these two types of lesion induced differential effects on the behavioural pattern either after saline or after D-amphetamine administration. Dopaminergic neurotransmission in the dorsal striatum plays a permissive role on the emergence of the behavioural responses, while the dorsal striatum circuitry plays a crucial role on the organization of the behavioural pattern. In addition, dopaminergic activity in this structure serves a primary control in the D-amphetamine-elicited motor activation or stereotypy, while the striatal structure is involved in the shaping of the D-amphetamine behavioural pattern.

Monoaminergic dysregulation on diestrus-2 and estrus through high emotional reactivity.

Rats with great differences in emotional reactivity, during weighing and handling for vaginal smear screening were examined on diestrus-2 (DE-2), proestrus (PE), and estrus (E). Rats with high emotional reactivity (HR), interpreted as trait anxiety, had different serotonergic and dopaminergic profile in hypothalamus-preoptic area (HY-PA) and striatum (Str) and thymus weight lower than that found in rats with low emotional reactivity (LR). In HY-PA of rats with HR when compared to rats with LR, increased 5-hydroxyindoleacetic acid (5-HIAA), 5-HIAA/serotonin (5-HT) ratio, and 3,4-dihydroxyphenylacetic acid (DOPAC) and in Str increased DOPAC and DOPAC/dopamine (DA) ratio were found only on DE-2, paralleled by increased adrenal weight and decreased thymus weight. In Str, a significant effect of HR on 5-HIAA was found only on E, in parallel with increased 5-HT and decreased DOPAC and DOPAC/DA ratio when compared to rats with LR. The results suggest that activation of 5-HT and DA in HY-PA and DA in Str through HR is apparent only on DE-2 while, conversely, on E suppression of striatal DA it is apparent with 5-HT dysregulation. These findings might have some relevance to the predisposition of women with trait anxiety to premenstrual syndrome.

Relationship between the thymus and neurochemical changes in the hypothalamus-preoptic area and prefrontal cortex in female rats with delayed puberty.

In female rats, aged 55-58 days with delayed puberty due to deficient growth and environmental stress, 5-hydroxyindoleacetic acid levels and serotonin turnover rate in the hypothalamus-preoptic area as well as body weight, body weight gain and relative weight of ovaries, uterus, adrenals and preputial glands were lower while serotonin and 5-hydroxyindoleacetic acid levels in the prefrontal cortex were higher when compared to normal rats with the latest onset of puberty aged 42-52 days. In rats with delayed puberty, multiple regression analysis revealed a significant negative dependence on dopamine turnover in the hypothalamus-preoptic area for body weight gain and, of all organs, for the relative weight of the thymus. A similar negative significant dependence on serotonin turnover rate in the prefrontal cortex was also found for the relative weight of thymus and spleen. The same analysis in the opposite direction revealed a significant negative dependence of 3,4-dihydroxyphenylacetic acid levels and dopamine turnover rate in the hypothalamus-preoptic area as well as serotonin turnover rate in the prefrontal cortex only on thymus weight. After separation of delayed pubertal rats into two groups, based on absolute ovarian weight, the rats in the low ovarian weight range and no signs of puberty exhibited: lower body weight gain, lower body weight, and lower relative weight only of thymus, ovaries and preputial glands in parallel with an increased dopamine turnover rate in the hypothalamus-preoptic area and serotonin turnover rate in the prefrontal cortex compared to the delayed pubertal rats in the high ovarian weight range and early signs of puberty. The results suggest that in rats with delayed puberty: (1) serotonergic activation in the hypothalamus-preoptic area is lower compared to normal puberty rats; (2) dopaminergic activation in the hypothalamus-preoptic area negatively affects body weight gain, thymus weight and initiation of puberty and (3) thymus weight is negatively implicated in dopaminergic activation in the hypothalamus-preoptic area and serotonergic activation in the prefrontal cortex and positively related to ovarian weight and early signs of puberty.

Risperidone: a novel antipsychotic with many "atypical" properties?

The acute and chronic administration effects of risperidone (Ris), a mixed 5HT2/D2 receptor antagonist, versus haloperidol (Hal) on dopaminergic and serotoninergic activity were investigated in the rat prefrontal cortex (Pfc), and the whole striatum (Str) as well as separately, in dorsal striatum (StrD) and nucleus accumbens (Acb). During acute administration, Hal was found to be more potent than Ris in increasing DA turnover rate in StrD. In contrast, during chronic administration, Ris but not Hal, continued to increase DA turnover activity in StrD. Moreover, in contrast to Hal, chronic Ris treatment continued to increase DA and 5-HT turnover rate in Pfc. These differential effects reveal that Hal does not share common characteristics with Ris with respect to its neurochemical profile in the Str and Pfc.

The neurochemical effects on striatal dopamine turnover rate of N-stearyl dopamine after acute administration in rats.

1. Considerable efforts have been made in order to develop autoreceptor selective agonists for the treatment of schizophrenia and hyperkinetic disorders. 2. Recent behavioural studies showed that the newly synthesized dopamine lipoamide, N-stearyl dopamine induced a strong hypomotility (-80%) in rats and mice. It is worth noting that this behavioural response was partially antagonized by dopaminergic antagonists, such as haloperidol and sulpiride, administered at doses that block DA autoreceptors. 3. In the present study the authors investigated the neurochemical changes induced by S-DA, in the striatum of the rat brain, in order to estimate a possible correlation between the above mentioned behavioural response and DA metabolism. 4. S-DA (10 or 100 mg/kg, i.p.) induced a significant decrease in DA turnover rate while it did not affect 5-HT metabolism in the striatum. 5. Considering that 5-DA induces a strong hypomotility, which can be partially antagonized by haloperidol or sulpiride administered at low doses, while also decreases the striatal DA turnover rate, it could be suggested that together these findings indicate that this DA lipoamide may be display the characteristics of an antipsychotic agent, acting on the "DA selective" autoreceptors.

The effect of sumatriptan on brain monoamines in rats.

Clinical data suggests that sumatriptan is effective in the acute treatment of migraine. The vascular effects of the drug have been invoked to explain this antimigraine efficacy. However, the effect of sumatriptan on brain monoamines has not previously been investigated. In order to study these hypothetical effects, we administered the drug to 24 male rats, subcutaneously, at three doses (0.3, 0.6, and 0.9 mg/kg of body weight), and 30 minutes later, all animals were decapitated. Dopamine, serotonin, and their metabolites 3,4 dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, and homovanillic acid concentrations were measured in the frontal cortex, hypothalamus, striatum, and hippocampus, by high performance liquid chromatography. Plasma concentrations of the drug were also determined. The control group was treated with NaCl 0.9%, given subcutaneously. Sumatriptan, at the dose of 0.3 mg/kg did not alter the brain monoamine concentrations; however, at the dose of 0.6 mg/kg, sumatriptan decreased serotonin concentration in the hypothalamus and increased the turnover of dopamine and serotonin in the hypothalamus and striatum, while at the dose of 0.9 mg/kg, it augmented only the turnover of serotonin in the hypothalamus. No dose-dependent effect of the drug was found. This subcortical antidopaminergic and antiserotoninergic effect of sumatriptan may be involved in its antimigraine action.

GABA-ergic mechanisms in the central control of cough.

The antitussive activity of gabalinoleamide (Gabalid U CB) was studied in 40 non-anaesthetized cats. The antitussive action of the substance was compared to that of codeine (Codein Spofa). Cough was induced by mechanical stimulation using a chronic tracheal cannula. Single cough parameters were evaluated from changes in the side tracheal pressure. When gabalinoleamide was administered in a dose of 100 mg/kg b.w. intramuscularly all the studied parameters of cough showed a statistically significant decrease, only the intensity of maximum cough effort remained unaffected. Gabalinoleamide administered in the same dose induced a statistically significant decrease of respiratory frequency and breathing amplitude, and prolonged the cycle of breathing by delaying the expiratory phase. Higher doses (200 and 300 mg/kg b.w.) did not have an increased cough suppressing effect. The quality and quantity of cough parameters were similar after codeine and gabalinoleamide.

Environmental lead pollution in Greece.

The blood lead concentration, an index of the environmental lead pollution, was measured in groups of individuals from many parts of greece. The mean blood lead value for urban area individuals was 27.03 micrograms/100 mL for adults, 32.30 for children and 31.03 for neonates; while for rural area individuals it was 18.81 micrograms/100 mL for adults, 22.98 for children and 21.66 for neonates. Twenty one percent of the urban individuals had laboratory evidence of "undue lead absorption" (blood lead level greater than 40 micrograms/100 mL) compared to 1.7% of the rural individuals. Children with elevated blood lead levels were found to have anemia.