Gender-dependent enhanced adult neurotoxic response to methamphetamine following fetal exposure to the drug. (41/446)

Methamphetamine use by females of child-bearing age has become a major public health concern in terms of the long-term risk to the exposed fetus. We examined the possibility of enhanced adult neurotoxic potential of the drug in offspring that had been exposed to methamphetamine in utero during gestational days 7 to 18. While basal levels of monoamines were not affected by prenatal exposure to methamphetamine, we observed an enhanced neurotoxicity in adult male offspring following drug challenge with effects localized primarily to the dopaminergic nigrostriatal projection. This was evidenced by greater methamphetamine-induced reductions of dopaminergic markers in the striatum [dopamine (DA), dihydroxyphenylacetic acid, homovanillic acid (HVA), and 3-methoxytyramine (3-MT)] and ventral brainstem (DA) of prenatal methamphetamine-treated males compared with saline-treated animals. Some effects of prenatal methamphetamine exposure were observed in female offspring, but these were limited to striatal levels of 3-MT and HVA. Differential gender sensitivity to the neurotoxic effect of methamphetamine was shown to be correlated with hyperthermic response. Hyperthermic effects, however, do not account for the increased susceptibility of prenatal methamphetamine-treated males to drug-induced striatal DA neurotoxicity since methamphetamine challenge did not evoke a significantly greater hyperthermic response in these animals compared with prenatal saline-treated males. The findings raise the concern that male methamphetamine abusers may be at risk for an enhanced neurotoxic risk if they were exposed to the drug in utero.  (+info)

Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release. (42/446)

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.  (+info)

Influence of different antidepressant drugs on the effect of chronic variable stress on restraint-induced dopamine release in frontal cortex. (43/446)

The aim of this study was to evaluate the influence of an early chronic variable stress procedure (CVS) associated or not with repeated administration of various antidepressants on cortical restraint-induced dopamine (DA) release in vivo. Animals were subjected to the CVS schedule and one day after submitted to persistent administration with vehicle, desipramine (DMI, 10 mg/kg, i.p.), fluoxetine (FLU, 10 mg/kg, i.p.) or phenelzine (PHE; 10 mg/kg, i.p.) and later on exposed to a 60-min restraint period. In addition, we also explored the effect of acute administration of these antidepressants on cortical DA overflow in response to restraint in CVS treated rats. A higher increase in cortical DA release in response to restraint was observed in CVS animals as compared with those without previous CVS. Persistent, but not acute, administration with DMI, FLU and PHE blocked the sensitized output induced by restraint following CVS exposure.  (+info)

Antagonism of nicotinic acetylcholine receptors by inhibitors of monoamine uptake. (44/446)

A study was made of the effects of several monoamine-uptake inhibitors on membrane currents elicited by acetylcholine (ACh-currents) generated by rat neuronal alpha2beta4 and mouse muscle nicotinic acetylcholine receptors (AChRs) expressed in Xenopus laevis oocytes. For the two types of receptors the monoamine-uptake inhibitors reduced the ACh-currents albeit to different degrees. The order of inhibitory potency was norfluoxetine > clomipramine > indatraline > fluoxetine > imipramine > zimelidine > 6-nitro-quipazine > trazodone for neuronal alpha2beta4 AChRs, and norfluoxetine > fluoxetine > imipramine > clomipramine > indatraline > zimelidine > trazodone > 6-nitro-quipazine for muscle AChRs. Thus, the most potent inhibitor was norfluoxetine, whilst the weakest ones were trazodone, 6-nitro-quipazine and zimelidine. Effects of the tricyclic antidepressant imipramine were studied in more detail. Imipramine inhibited reversibly and non-competitively the ACh-current with a similar inhibiting potency for both neuronal alpha2beta4 and muscle AChRs. The half-inhibitory concentrations of imipramine were 3.65 +/- 0.30 microM for neuronal alpha2beta4 and 5.57 +/- 0.19 microM for muscle receptors. The corresponding Hill coefficients were 0.73 and 1.2 respectively. The inhibition of imipramine was slightly voltage-dependent, with electric distances of approximately 0.10 and approximately 0.12 for neuronal alpha2beta4 and muscle AChRs respectively. Moreover, imipramine accelerated the rate of decay of ACh- currents of both muscle and neuronal AChRs. The ACh-current inhibition was stronger when oocytes, expressing neuronal alpha2beta4 or muscle receptors, were preincubated with imipramine alone than when it was applied after the ACh-current had been generated, suggesting that imipramine acts also on non-activated or closed AChRs. We conclude that monoamine-uptake inhibitors reduce ACh-currents and that imipramine regulates reversibly and non- competitively neuronal alpha2beta4 and muscle AChRs through similar mechanisms, perhaps by interacting externally on a non-conducting state of the AChR and by blocking the open receptor-channel complex close to the vestibule of the channel. These studies may be important for understanding the regulation of AChRs as well as for understanding antidepressant- and side-effects of monoamine-uptake inhibitors.  (+info)

Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue. (45/446)

The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.  (+info)

Changes in monoamine release in the ventral horn and hypoglossal nucleus linked to pontine inhibition of muscle tone: an in vivo microdialysis study. (46/446)

A complete suppression of muscle tone in the postural muscles and a reduction of muscle tone in the respiratory related musculature occur in rapid eye movement (REM) sleep. Previous studies have emphasized the role of glycine in generating these changes. Because the activity of norepinephrine- and serotonin-containing neurons is known to decrease in REM sleep, we hypothesized that a decrease in release in one or both of these transmitters might be detected at the motoneuronal level during muscle tone suppression elicited by brainstem stimulation in the decerebrate animal. We compared release in the ventral horn with that in the hypoglossal nucleus to determine whether the mechanism of muscle tone suppression differs in these nuclei as has been hypothesized. Electrical stimulation and cholinergic agonist injection into the mesopontine reticular formation produced a suppression of tone in the postural and respiratory muscles and simultaneously caused a significant reduction of norepinephrine and serotonin release of similar magnitude in both hypoglossal nucleus and spinal cord. Norepinephrine and serotonin release in the motoneuron pools was unchanged when the stimulation was applied to brainstem areas that did not generate bilateral suppression. No change in dopamine release in the motoneuron pools was seen during mesopontine stimulation-induced atonia. We hypothesize that the reduction of monoamine release that we observe exerts a disfacilitatory effect on both ventral horn and hypoglossal motoneurons and that this disfacilitatory mechanism contributes to the muscle atonia elicited in the decerebrate animal and in the intact animal during REM sleep.  (+info)

Determination of effects of antiepileptic drugs on SNAREs-mediated hippocampal monoamine release using in vivo microdialysis. (47/446)

1. To elucidate possible mechanisms underlying the effects of carbamazepine (CBZ), valproate (VPA) and zonisamide (ZNS) on neurotransmitter exocytosis, the interaction between these three antiepileptic drugs (AEDs) and botulinum toxins (BoNTs) on basal, Ca(2+)- and K(+)-evoked release of dopamine (DA) and serotonin (5-HT) were determined by microdialysis in the hippocampus of freely moving rats. 2. Basal release of monoamine was decreased by pre-microinjection of the syntaxin inhibitor, BoNT/C, but only weakly affected by the synaptobrevin inhibitor, BoNT/B. Ca(2+)-evoked release was inhibited by BoNT/C selectively. K(+)-evoked release was reduced by BoNT/B predominantly and BoNT/C weakly. 3. Perfusion with low and high concentrations of CBZ and ZNS increased and decreased basal monoamine release, respectively. Perfusion with VPA increased basal 5-HT release concentration-dependently, whereas basal DA release was affected by VPA biphasic concentration-dependently, similar to CBZ and ZNS. This stimulatory action of AEDs on basal release was inhibited by BoNT/C predominantly. 4. Ca(2+)-evoked monoamine release was increased by low concentrations of CBZ, ZNS and VPA, but decreased by high concentrations. These effects of the AEDs on Ca(2+)-evoked release were inhibited by BoNT/C, but not by BoNT/B. 5. K(+)-evoked monoamine release was reduced by AEDs concentration-dependently. The inhibitory effect of these three AEDs on K(+)-evoked release was inhibited by BoNT/B, but not by BoNT/C. 6. These findings suggest that the therapeutic-relevant concentration of CBZ, VPA and ZNS affects exocytosis of DA and 5-HT, the enhancement of syntaxin-mediated monoamine release during resting stage, and the inhibition of synaptobrevin-mediated release during depolarizing stage.  (+info)

Circadian regulation of gene expression systems in the Drosophila head. (48/446)

Mechanisms composing Drosophila's clock are conserved within the animal kingdom. To learn how such clocks influence behavioral and physiological rhythms, we determined the complement of circadian transcripts in adult Drosophila heads. High-density oligonucleotide arrays were used to collect data in the form of three 12-point time course experiments spanning a total of 6 days. Analyses of 24 hr Fourier components of the expression patterns revealed significant oscillations for approximately 400 transcripts. Based on secondary filters and experimental verifications, a subset of 158 genes showed particularly robust cycling and many oscillatory phases. Circadian expression was associated with genes involved in diverse biological processes, including learning and memory/synapse function, vision, olfaction, locomotion, detoxification, and areas of metabolism. Data collected from three different clock mutants (per(0), tim(01), and Clk(Jrk)), are consistent with both known and novel regulatory mechanisms controlling circadian transcription.  (+info)