Transgenerational effects of maternal obesity and gestational diabetes on offspring body composition and left ventricle mass: the Finnish Gestational Diabetes Prevention Study (RADIEL) 6-year follow-up.

AIM: To investigate the influence of maternal adiposity and gestational diabetes on offspring body composition and left ventricle mass in early childhood. METHODS: The observational follow-up study included 201 mother-child pairs, a sub-cohort from the Finnish Gestational Diabetes Prevention Study, who were recruited 6.1 ± 0.5 (mean ± SD) years postpartum, aiming for an equal number of mothers with and without gestational diabetes. RESULTS: Maternal pre-pregnancy BMI (mean ± SD; 30.5 ± 5.6 kg/m2 ) was associated with child body fat percentage [0.26 (95% CI; 0.08, 0.44)% increase in child body fat per 1 kg/m2 increase in pre-pregnancy BMI of mothers with obesity] and was reflected in child BMI Z-score (mean ± SD; 0.45 ± 0.93). Left ventricle mass, left ventricle mass index and left ventricle mass Z-score were not associated with gestational diabetes, pre-pregnancy BMI or child body fat percentage. After adjusting for child sex, body fat percentage, systolic blood pressure, pre-pregnancy BMI and maternal lean body mass, left ventricle mass increased by 3.08 (95% CI; 2.25, 3.91) g for each 1 kg in child lean body mass. CONCLUSIONS: Left ventricle mass at 6 years of age is determined predominantly by lean body mass. Maternal pre-gestational adiposity is reflected in child, but no direct association between left ventricle mass and child adiposity or evidence of left ventricle mass foetal programming related to gestational diabetes and maternal adiposity was observed in early childhood.

Seroquel: electrophysiological profile of a potential atypical antipsychotic.

Extracellular single unit recording techniques were employed to compare the effects of seroquel with the reference antipsychotic (AP) agents clozapine and haloperidol in electrophysiological tests that may predict AP activity. Seroquel and clozapine were differentially more active in reversing the inhibitory actions of d-amphetamine on mesolimbic (A10) than nigrostriatal (A9) dopamine (DA)-containing neurons, whereas haloperidol exhibited the opposite selectivity. In cell population studies, acute treatment with seroquel and clozapine selectively increased the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarization inactivation (DI) of A10 DA cells following repeated (28 day) administration. This profile of activity was unlike that of haloperidol, which acutely caused a nonselective increase in the number of active A9 and A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after repeated treatment. Since DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects (EPS) and tardive dyskinesia (TD), seroquel, like clozapine, may be an atypical AP with a reduced likelihood for producing EPS/TD.

NBQX is a selective non-NMDA receptor antagonist in rat hippocampal slice.

The effects of NBQX and DNQX on synaptic transmission in rat hippocampal slice were investigated. Both agents produced dose-dependent blockade of field potentials evoked by low frequency stimulation of Schaffer collateral-commissural fibers recorded in medium containing 4 mM Mg2+ (non-NMDA mediated transmission), with half-maximal effects at about 0.15 microM for NBQX and 1.0 microM for DNQX. When the studies were conducted in Mg(2+)-free medium (predominantly NMDA mediated transmission), 100 microM NBQX failed to block transmission; however, the response could be completely blocked by the addition of 10 microM of the competitive NMDA antagonist CPP. In contrast, 47 microM DNQX completely blocked secondary field potentials recorded in Mg(2+)-free medium and this effect could be reversed by the addition of 200 microM of the glycine agonist D-serine. Thus, NBQX exhibited selective blockade of non-NMDA mediated synaptic transmission whereas DNQX had effects at both non-NMDA and NMDA receptor sites, the latter effect via an interaction with the glycine site on the NMDA receptor complex.

Effects of ICI 169,369, a selective serotonin2 antagonist, in electrophysiological tests predictive of antipsychotic activity.

Extracellular single unit recording techniques were used to compare the effects of ICI 169,369, a selective serotonin2 receptor antagonist, with the reference antipsychotic (AP) agents clozapine and haloperidol, in electrophysiological tests that may predict AP activity. ICI 169,369 was found to reverse the inhibitory actions of amphetamine on A9 and A10 dopamine (DA) neurons, a common property shared by other AP drugs, and was comparable in potency to clozapine. In cell population studies, acute treatment with ICI 169,369 (at a low dose only) and clozapine selectively increased the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarization inactivation (DI) of A10 DA cells after chronic administration. Interestingly, chronic treatment with ICI 169,369 also caused a significant increase in the number of actively discharging A9 DA cells, an effect not predicted on the basis of the acute data. A similar effect was noted for clozapine, although the magnitude did not reach statistical significance. This profile of activity was unlike that of haloperidol, which acutely caused a nonselective increase in the number of active A9 and A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after chronic treatment. Inasmuch as DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects, ICI 169,369, like clozapine, may be a potential AP with a reduced likelihood for producing extrapyramidal side effects.

Spontaneous activity of A9 and A10 dopamine neurons after acute and chronic administration of the selective dopamine D-1 receptor antagonist SCH 23390.

The effects of acute and chronic treatment with the selective dopamine (DA) D-1 antagonist SCH 23390 on the population response of midbrain DA cells were determined. One hour pretreatment with SCH 23390 (0.0125, 0.025, 0.05 mg/kg s.c.) caused a dose-related increase in the number of spontaneously firing DA neurons in both the A9 and A10 cell regions. Chronic (28 day) administration of SCH 23390 (0.05 mg/kg s.c.) caused depolarization inactivation of only A10 DA cells. These data suggest that SCH 23390 may have antipsychotic properties with a reduced likelihood of producing extrapyramidal side effects.

D-2 dopamine antagonist-like effects of SCH 23390 on A9 and A10 dopamine neurons.

The effects of SCH 23390 on d-amphetamine-induced suppression of A9 and A10 DA neuronal firing were determined. SCH 23390 potently reversed d-amphetamine on both A9 and A10 DA neurons. Compared to haloperidol, SCH 23390 was 5 times more potent on A9 DA neurons and 20 times more potent on A10 DA neurons. However, the magnitude of the reversal effect was greater with haloperidol than SCH 23390. In addition, haloperidol produced a further increase in firing of both A9 and A10 DA neurons after SCH 23390 maximally increased firing. It was concluded that SCH 23390 has D-2 DA antagonist-like properties, possibly mediated via an interaction at D-1 DA receptors, which may be functionally linked with D-2 DA receptors. The marked potency of SCH 23390 in reversing d-amphetamine could be due to its combined antagonist effects at 5HT2 and D-1 DA receptor sites.

Behavioral evidence for beta-adrenoceptor subsensitivity after subacute antidepressant/alpha 2-adrenoceptor antagonist treatment.

The behavioral consequences of beta-adrenoceptor subsensitivity were investigated by determining whether a physiological response that is mediated by beta-receptors, isoproterenol-induced drinking (IID), would be reduced by subacute antidepressant/alpha 2-antagonist treatment. The coadministration of typical (e.g., imipramine) or atypical (e.g., mianserin) antidepressants with yohimbine or piperoxan twice daily for four consecutive days reduced IID. Both the time course as well as the magnitude of beta-adrenoceptor subsensitivity could be behaviorally demonstrated. In addition, the reduction in IID observed after coadministration of imipramine with yohimbine was a centrally mediated effect since it was observed after systemic (subcutaneous) and central (intraventricular) administration of isoproterenol. These results provide evidence that IID is an appropriate behavioral model to demonstrate beta-adrenoceptor subsensitivity following subacute antidepressant/alpha 2-antagonist treatment.