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At least 1,315 records · Page 73Linked to original sources
PubMed1997

Cholecystokinin, dopamine D2 and N-methyl-D-aspartate binding sites in the nucleus of the solitary tract of the rat: possible relationship to ingestive behavior.

Receptor autoradiography was used to investigate the distribution of brainstem binding sites for cholecystokinin, dopamine and N-methyl-D-aspartate with particular reference to the nucleus of the solitary tract of the rat, an area involved in the control of ingestive behavior. Binding sites for the A and B subtypes of the cholecystokinin receptor, labeled with [(125)I]cholecystokinin octapeptide sulfate in the presence or absence of antagonists for the devazepide (A) or L-365,260 (B) receptor, were present throughout the caudal rostral extent of the nucleus of the solitary tract, the A type predominating in the commissural, medial and gelatinous part and the B type in the lateral part. In the most rostral part of the medial nucleus of the solitary tract, both A and B receptors were present. Dopamine D2 receptors, labeled with [(125)I]NCQ-298, were found in all parts of the nucleus of the solitary tract. No binding to the dopamine D1 receptor, labeled with [(125)I]SCH-23982, was found in the brainstem. N-Methyl-D-aspartate receptors, labeled with [(3)H]dizocilpine maleate, were also present in the entire caudorostral extent of the nucleus of the solitary tract. Binding to cholecystokinin A receptors was co-distributed with [(125)I]NCQ-298 and [(3)H]dizocilpine maleate binding in the caudal and rostral parts of the nucleus of the solitary tract, and binding to cholecystokinin B receptors overlapped with [(125)I]NCQ-298 and [(3)H]dizocilpine maleate binding in the rostral nucleus of the solitary tract. These results are consistent with the hypothesis that cholecystokinin, dopamine and glutamate interact in the nucleus of the solitary tract in the control of ingestive behavior.

Animals↗
PubMed1997

Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment.

Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D3 receptors was not changed in any brain region by any of the drug treatments. [3H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [3H]nemonapride and [3H]spiperone binding to dopamine D2-like receptors in the caudate putamen. In contrast, haloperidol caused a small, significant increase in [3H]raclopride binding in the lateral caudate putamen only. Raclopride also elevated, but to a lesser extent [3H]nemonapride and [3H]spiperone binding in caudate putamen, whereas it did not affect [3H]raclopride binding. Clozapine did not significantly change D2-like striatal binding of [3H]nemonaipride, [3H]spiperone or [3H]raclopride. The differences in radioligand binding suggest that [3H]nemonapride and [3H]spiperone may be binding to additional subsets of dopamine D2-like receptors (including D4-like receptors) that are not recognized by [3H]raclopride, which has high affinity for D2 and D3 receptors only. Quantification of [3H]nemonapride or [3H]spiperone binding in the presence of 300 nM raclopride (to block D2 and D3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D4-like receptors in the caudate putamen using either radioligand. These results suggest that D4-like receptors may be a common site of action of both typical and atypical antipsychotics.

Animals↗
PubMed1997

Dopaminergic modulation of mitral cell activity in the frog olfactory bulb: a combined radioligand binding-electrophysiological study.

Dopamine content in the amphibian olfactory bulb is supplied by interneurons scattered among mitral cells in the external plexiform/mitral cell layer. In mammals, dopamine has been found to be involved in various aspects of bulbar information processing by influencing mitral cell odour responsiveness. Dopamine action in the bulb depends directly on the localization of its receptor targets, found to be mainly of the D2 type in mammals. The present study assessed, in the frog, both the anatomical localization of D2-like, radioligand-labelled receptors of dopamine and the in vivo action of dopamine on unitary mitral cell activity in response to odours delivered over a wide range of concentrations. The [125I]iodosulpride-labelled D2 binding sites were visualized on frozen sagittal sections of frog brains by film radioautography. The sites were found to be restricted to the external plexiform/mitral cell layer; other layers of the olfactory bulb were devoid of specific labelling. Electrophysiological recordings of mitral unit activity revealed that dopamine or its agonist apomorphine induced a drastic reduction of spontaneous firing rate of mitral cells in most cases without altering odour intensity coding properties of these cells. Moreover, pre-treatment with the D2 antagonist eticlopride blocked the dopamine-induced reduction of mitral cell spontaneous activity. In the frog olfactory bulb, both anatomical localization of D2-like receptors and functional data on dopamine involvement in information processing differ from those reported in mammals. This suggests a phylogenetic evolution of dopamine action in the olfactory bulb. In the frog, anatomical data perfectly corroborate electrophysiological results, together strongly suggesting a direct action of dopamine on mitral cells. In a physiologically operating system, such an action would result in a global improvement of signal-to-noise ratio.

Animals↗
PubMed1997

Apomorphine priming alters the response of striatal outflow pathways to D2 agonist stimulation in 6-hydroxydopamine-lesioned rats.

Chronic treatment with dopaminergic agonists is associated with response fluctuations to L-dihydroxyphenylalanine in Parkinson's disease and enhanced motor activity to D1 and D2 dopamine agonists in rats with 6-hydroxydopamine lesions of the nigrostriatal pathway. In dopamine-depleted rodents this phenomenon has been referred to as "priming" or reverse tolerance. The neurochemical changes that underlie "priming" of dopaminergic agonist responses are poorly understood. Some aspects of priming of D1 agonist-mediated rotation in the 6-hydroxydopamine-lesioned rat have been characterized, but priming of D2-agonist-dependent motor responses has been less thoroughly studied. In this study, examination of rotational behaviour and induction of Fos-like immunoreactivity were used to investigate changes in the striatal outflow systems in response to treatment with the D2 agonist quinpirole in 6-hydroxydopamine-lesioned rats that had been primed with apomorphine. Administration of apomorphine (0.5 mg/kg; three injections at three to six day intervals) permitted an otherwise inactive dose of quinpirole (0.25 mg/kg) to produce robust contralateral rotation and to induce the expression of Fos in striatal neurons belonging to the striato-nigro-entopeduncular ("direct") pathway. The increase in contralateral rotation and ipsilateral striatal Fos expression following administration of quinpirole to apomorphine-primed rats was mediated by a D2-like receptor and did not appear to be due to a change in sensitivity of D2 receptors. Apomorphine priming also enhanced the ability of quinpirole to induce Fos expression in the globus pallidus, a target of the striatopallidal ("indirect") pathway. Western blot analysis confirmed that treatment with quinpirole induced the expression of c-Fos protein with no change in the expression of 35-37,000 mol. wt Fos-related antigens in apomorphine-primed rats treated with water or quinpirole. Induction of Fos expression in the striatum generally results from blockade of D2 receptors and the striato-nigro-entopeduncular pathway preferentially expresses D1 receptors. Thus, the quinpirole-dependent induction of striatal Fos in apomorphine-primed 6-hydroxydopamine-lesioned rats represents a qualitative alteration in striatal outflow. These studies demonstrate that pretreatment of 6-hydroxydopamine-lesioned rats with apomorphine increases the activity of the "direct" and "indirect" striatal outflow pathways in response to D2 receptor stimulation. These changes have the net result of enhancing thalamocortical activity and likely underlie the enhanced contralateral rotation produced by quinpirole in apomorphine-primed rats. Changes in striatal outflow, particularly in the striato-nigro-entopeduncular pathway, may contribute to alterations in D2-dependent motor responses observed after chronic dopaminergic stimulation in the dopamine-depleted striatum.

Animals↗
PubMed1997

Differing influences of dopamine agonists and antagonists on Fos expression in identified populations of globus pallidus neurons.

Dopamine agonists increase the activity of globus pallidus neurons, as shown electrophysiologically and with Fos expression. More recently it has been shown that decreased D2 receptor activity also causes pallidal Fos expression. Similar responses occur in the striatum, where both dopamine agonists and D2 blockade induce Fos, although in separate neuronal populations (i.e. striatonigral and -pallidal). The present experiments investigate the possible differential dopaminergic regulation of Fos within pallidal neuronal populations, which were classified as parvalbumin-positive or -negative (with parvalbumin immunostaining), or as projecting to various target nuclei (with retrograde transport of FluoroGold iontophoresed into these nuclei). Rats with prior nigrostriatal lesions received saline, D1 agonist, or D2 agonist. Rats with no lesions received saline, combined D1/D2 agonists, or the D2 antagonist eticlopride. Two hours after drug injection, rats were perfused and their brains processed for double-labeling: either Fos staining with parvalbumin staining, or Fos or parvalbumin staining in FluoroGold-labeled sections. Overall, dopamine drug treatments induced more Fos in parvalbumin-negative than -positive cells. However, unlike dopamine agonists, eticlopride induced significant Fos only in the parvalbumin-negative cells. Dopamine agonist-induced Fos was found in pallidal neurons projecting to each of the target nuclei examined, in both normal and nigrostriatal-lesioned rats. Eticlopride-induced Fos occurred only in pallidal neurons projecting to the striatum, providing functional evidence for pallidostriatal cells without axon collaterals to other nuclei. It was also found that pallidostriatal neurons were distinguished from other projection populations by a relative lack of parvalbumin immunoreactivity. Pallidal cells respond heterogeneously to dopaminergic treatments based on their projection target and expression of parvalbumin. The smaller Fos responses in parvalbumin-containing cells may be due largely to the calcium buffering by the parvalbumin itself. Also, the pattern of Fos expression in pallidostriatal neurons suggests that dopamine regulates activity in these cells differently than in other projection populations.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Distribution and postnatal ontogeny of adenosine A2A receptors in rat brain: comparison with dopamine receptors.

In adult rat brain, adenosine A2A receptors and dopamine D2 receptors are known to be located on the same cells where they interact in an antagonistic manner. In the present study we wanted to examine when this situation develops and compared the postnatal ontogeny of the binding of the adenosine A2A receptor agonist [3H]CGS 21680, the binding of the dopamine D1 receptor antagonist [3H]SCH 23390 and the dopamine D2 receptor antagonist [3H]raclopride. All three radioligands bound to the striatum at birth and this binding increased several-fold during the postnatal period. [3H]SCH 23390 binding developed first (mostly during the first week), followed by [3H]raclopride binding (first to third week) and [3H]CGS 21680 binding (only during second and third week). For all three radioligands the binding tended to decrease between 21 days and adulthood. This occurred earlier and was more pronounced in the globus pallidus than in the other examined structures. The increase in [3H]CGS 21680 binding from newborn to adult was mainly due to four-fold increase in the number of binding sites. The pharmacology of [3H]CGS 21680 binding to caudate-putamen was similar in newborn, one-week-old and adult animals, and was indicative of A2A receptors. The binding was inhibited by guanylyl imidodiphosphate at all ages, indicating that A2A receptors are G-protein-coupled already at birth. In contrast to the large increase in [3H]CGS 21680 binding, there was a decrease in the levels of A2A messenger RNA during the postnatal period in the caudate-putamen. In cerebral cortex [3H]CGS 21680 bound to a different site than the A2A receptor. From birth to adulthood cortical binding of [3H]CGS 21680 increased four-fold and that of the adenosine A1 agonist [3H]cyclohexyladenosine 19-fold. During early postnatal development [3H]SCH 23390 binding was higher in deep than in superficial cortical layers, but this difference disappeared in adult animals. There was binding of both [3H]CGS 21680 and [3H]cyclohexyladenosine to the olfactory bulb, suggesting a role of the two adenosine receptors in processing of olfactory information. [3H]CGS 21680 binding was present in the external plexiform layer and glomerular layer, and increased during development, but the density of binding sites was about one tenth of that seen in caudate putamen. [3H]cyclohexyladenosine showed a very different labelling pattern, resembling that observed with [3H]SCH 23390. Postnatal changes in adenosine receptors may explain age-dependent differences in stimulatory caffeine effects and endogenous protection against seizures. Since A2A receptors show a co-distribution with D2 receptors throughout development, caffeine may partly exert such actions by regulating the activity of D2 receptor-containing striatopallidal neurons.

Adenosine↗
PubMed1997

A functional interaction between the mesolimbic dopamine system and vasopressin release in the regulation of blood pressure in conscious rats.

The aim of the present study was to further characterize the involvement of the mesolimbic dopamine system in central blood pressure regulation, with particular emphasis on the interaction of this system with the effects of circulating vasopressin. In conscious rats we stimulated the release of endogenous dopamine from mesolimbic/mesocortical terminals by administration of the substance P analogue DiMe-C7 ([pGlu5, MePhe8, Sar9]-Substance P5-11; 10 nmol) into the ventral tegmental area. Chemical stimulation of the ventral tegmental area resulted in a significant increase in blood pressure and heart rate. These effects were prevented by either bilateral electrolytic lesions of the hypothalamic supraoptic nucleus or by systemic pretreatment with the dopamine D2 receptor antagonist raclopride (0.5 mg/kg). Stimulation of the ventral tegmental area also produced a marked increase in the expression of the proto-oncogene c-fos in the supraoptic nucleus and a significant increase in plasma vasopressin levels, suggesting activation of vasopressinergic neurons in this nucleus. However, this effect of stimulation of the ventral tegmental area was not significantly inhibited by pretreatment with raclopride. We suggest that the effects on blood pressure and heart rate of stimulation of the ventral midbrain by micro-injection of DiMe-C7 are the result of combined activation of both dopaminergic and non-dopaminergic cell bodies in this region. Stimulation of non-dopaminergic cells in the ventral midbrain may induce a moderate increase in plasma vasopressin levels by activation of the supraoptic nucleus. An additional stimulation of dopaminergic cells in the ventral midbrain allows the increase in circulating vasopressin levels to become manifest as a pressor response, possibly by inhibition of vasopressin-induced facilitation of baroreflex responses.

Animals↗
PubMed1998

Simultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely-moving rats reveals a complex pattern of reciprocal auto- and heteroreceptor-mediated control of release.

In the present study, a novel and exceptionally sensitive method of high-performance liquid chromatography coupled to coulometric detection, together with concentric dialysis probes, was exploited for an examination of the role of autoreceptors and heteroceptors in the modulation of dopamine, noradrenaline and serotonin levels in single samples of the frontal cortex of freely-moving rats. The selective D3/D2 receptor agonist, CGS 15855A [(+/-)-trans-1,3,4,4a,5,10b-hexahydro-4-propyl-2H-[1]benzopyrano[3 ,4-b]-pyridin-9-ol], and antagonist, raclopride, respectively decreased (-50%) and increased (+60%) levels of dopamine without significantly modifying those of serotonin and noradrenaline. The selective alpha2-adrenergic receptor agonist, dexmedetomidine, markedly decreased noradrenaline levels (-100%) and likewise suppressed those of serotonin and dopamine by -55 and -45%, respectively. This effect was mimicked by the preferential alpha2-adrenergic receptor agonist, guanabenz (-100%, -60% and -50%). Furthermore, the alpha2-adrenergic receptor antagonist, RX 821,002 [2(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline], and the preferential alpha2A-adrenergic receptor antagonist, BRL 44408 [2-(2H-(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidaz ole], both evoked a pronounced elevation in levels of noradrenaline (+212%, +109%) and dopamine (+73%, +85%). In contrast, the preferential alpha(2B/2C)-adrenergic receptor antagonist, prazosin, did not modify noradrenaline and dopamine levels. RX 821,002 and BRL 44408 did not significantly modify levels of serotonin, whereas prazosin decreased these levels markedly (-55%), likely due to its alpha1-adrenergic receptor antagonist properties. The selective serotonin-1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), reduced serotonin levels (-65%) and increased those of dopamine and noradrenaline by +100%), and +175%, respectively. The selective serotonin-1A antagonist, WAY 100,635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo- hexanecarboxamide], which had little affect on monoamine levels alone, abolished the influence of 8-OH-DPAT upon serotonin and dopamine levels and significantly attenuated its influence upon noradrenaline levels. Finally, the selective serotonin-1B agonist, GR 46611 [3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamid e], decreased serotonin levels (-49%) and the serotonin-1B antagonist, GR 127,935 [N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4-oxadiazol-3-yl)-biphenyl-4-carboxamide], which did not significantly modify serotonin levels alone, abolished this action of GR 46611. Levels of dopamine and noradrenaline were not affected by GR 46611 or GR 127,935. In conclusion, there is a complex pattern of reciprocal autoreceptor and heteroceptor control of monoamine release in the frontal cortex. Most notably, activation of alpha2-adrenergic receptors inhibits the release of noradrenaline, dopamine and serotonin in each case, while stimulation of serotonin-1A receptors suppresses serotonin, yet facilitates noradrenaline and dopamine release. In addition, dopamine D2/D3 autoreceptors restrain dopamine release while (terminal-localized) serotonin-1B receptors reduce serotonin release. Control of serotonin release is expressed phasically and that of noradrenaline and dopamine release tonically.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

The effects of globus pallidus lesions on dopamine-dependent motor behaviour in rats.

Motor effects of bilateral lesions of the globus pallidus induced by quinolinic acid (30 and 60 nmol in 0.5 microl) were investigated in rats. Globus pallidus lesions with 60 nmol quinolinic acid produced a significant reduction of spontaneous motor activity measured by a reduced locomotor activity in an open field and by a reduced sniffing activity in an experimental chamber. In addition, D-amphetamine (1 mg/kg, i.p.)-induced hyperlocomotion and D-amphetamine (3 mg/kg, i.p.)-induced stereotyped sniffing were significantly reduced in animals with quinolinic acid lesions (60 nmol). Globus pallidus lesions with 60 nmol quinolinic acid potently reversed catalepsy induced by systemic administration of the dopamine D1 receptor antagonist SCH23390 (0.75 and 1 mg/kg, i.p.) or the dopamine D2 receptor antagonist raclopride (1.25 and 5 mg/kg, i.p.), while lesions with 30 nmol quinolinic acid exerted anti-cataleptic effects which were only partly significant. In line with current models of basal ganglia functions, these findings indicate that inactivation of the globus pallidus reduced spontaneous motor activity and motor hyperactivity after dopamine receptor stimulation. However, the present data also demonstrate that inactivation of the globus pallidus reversed motor hypoactivity induced by a blockade of dopamine D1 and D2 receptors. Therefore, a more complex functional model of the globus pallidus is required to account for the opposite effects on motor behaviour observed after lesions of this basal ganglia nucleus.

Animals↗
PubMed1999

Enkephalin regulates acute D2 dopamine receptor antagonist-induced immediate-early gene expression in striatal neurons.

Projection neurons of the striatum release opioid peptides in addition to GABA. Our previous studies showed that the opioid peptide dynorphin regulates that subtype of projection neurons which sends axons to the substantia nigra/entopeduncular nucleus, as indicated by an inhibitory action of dynorphin/agonists on D1 dopamine receptor-mediated immediate-early gene induction in these neurons. The other subtype of striatal projection neurons projects to the globus pallidus and contains the opioid peptide enkephalin. Here, we investigated whether enkephalin regulates the function of striatopallidal neurons, by analysing opioid effects on immediate-early gene induction by D2 dopamine receptor blockade that occurs in these neurons. Thus, the effects of systemic and intrastriatal administration of various opioid receptor agonists and antagonists on immediate-early gene expression (c-fos, zif 268) induced by the D2 receptor antagonist eticlopride were examined with in situ hybridization histochemistry. Intrastriatal infusion of enkephalin (delta and mu), but not dynorphin (kappa), receptor agonists suppressed immediate-early gene induction by eticlopride in a dose-dependent manner. This suppression was blocked by the opioid receptor antagonist naloxone, confirming the involvement of opioid receptors. Repeated treatment with D2 receptor antagonists produces increased enkephalin expression and diminished immediate-early gene inducibility in striatopallidal neurons, as well as behavioral effects that are attenuated compared to those of acute treatment (e.g., reduced akinesia). Naloxone reversed such behavioral recovery (i.e. reinstated akinesia), but did not significantly affect suppressed immediate-early gene induction. Our results indicate that enkephalin acts, via mu and delta receptors in the striatum, to inhibit acute effects of D2 receptor blockade in striatopallidal neurons. Moreover, the present findings suggest that increased enkephalin expression after repeated D2 receptor antagonist treatment is an adaptive response that counteracts functional consequences of D2 receptor blockade, but is not involved in suppressed immediate-early gene induction. Together with our earlier findings of the role of dynorphin, these results indicate that opioid peptides in the striatum serve as negative feedback systems to regulate the striatal output pathways in which they are expressed.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Ventral hippocampal dopamine D1 and D2 systems and spatial working memory in rats.

The hippocampus has long been known to be important for memory function. However, the involvement of hippocampal dopamine systems with memory has received little attention. In the current study, dopamine D1 and D2 hippocampal receptor system involvement with memory was assessed in female Sprague-Dawley rats by local infusion of D1 and D2 agonists and antagonists into the ventral hippocampus. Working memory performance was assessed on the radial-arm maze. Neither the D1 agonist dihydrexidine (1.1-10 microg/side) nor the D1 antagonist SCH 23390 (0.19-1.67 microg/side) was effective in significantly altering radial-arm maze choice accuracy. In contrast, there were significant and opposite effects of D2 agonist and antagonist treatments. The D2 agonist quinpirole caused a significant (P<0.05) dose-related improvement in choice accuracy over a dose range of 1.1-10 microg/side. In a complementary fashion, the D2 antagonist raclopride caused a significant (P<0.05) dose-related choice accuracy deficit over a range of 0.19-1.67 microg/side. This study provides clear evidence that hippocampal D2 activity is positively related to working memory performance, while evidence for D1 systems is less compelling. Dopamine D2 receptors in the ventral hippocampus were shown to have important influences on spatial working memory. In a consistent pattern of effects ventral hippocampal infusion of the D2 agonist quinpirole improved working memory performance in the radial-arm maze, while ventral hippocampal infusion of the D2 antagonist raclopride impaired performance.

Animals↗
PubMed1999

Dopamine receptor coupling to adenylyl cyclase in rat olfactory pathway: a combined pharmacological-radioautographic approach.

Dopamine binding sites of D1 and D2/D3 subtypes had been detected in the rat peripheral olfactory system and postulated to account for dopamine-dependent enhancement of olfactory memory and retro-inhibition of olfactory input within the olfactory bulb, respectively. We further assessed, in the present study, the mechanisms of these dopamine actions by using adenylyl cyclase activity assay and [35S]GTP radioautography in rat olfactory bulb and mucosa. The D1 agonist SKF 38393 increased adenylyl cyclase activity on membranes of the olfactory bulb, but not on those of the olfactory mucosa. Stimulation of adenylyl cyclase by SKF 38393 in the olfactory bulb was dose dependent, with a half-maximal effect (EC50) at 0.16 microM SKF 38393, reaching 40% over basal adenylyl cyclase activity, and was blocked by the D1 antagonist SCH 23390. The D2 agonists bromocriptine and quinpirole inhibited both basal and forskolin-stimulated adenylyl cyclase activities in the olfactory bulb and mucosa. These adenylyl cyclase inhibitions were dose dependent, with EC50 values of 0.1-0.3 microM for bromocriptine and 1-3 microM for quinpirole, equal to 25% of basal enzyme activity at concentrations of 1-10 microM, and were blocked by the D2 antagonist eticlopride. The D2 antagonist was devoid of any effect on basal and forskolin-stimulated adenylyl cyclase activities in the olfactory bulb and mucosa. Odorant-induced stimulation of adenylyl cyclase was blocked by D2 agonist in olfactory mucosa membranes, which suggests dopaminergic regulation of odor detection in the olfactory mucosa. By using microdissected fractions of the olfactory mucosa, D2 agonist-induced inhibition of adenylyl cyclase was shown to occur only in lamina propria, thus co-localizing with D2 binding sites. [35S]GTP radioautography on tissue sections revealed D2 agonist-induced G-protein activation in olfactory nerve and glomerular layers of the olfactory bulb, and in the chorion of the olfactory mucosa. Taken together, these data demonstrate functional coupling of the dopamine receptors with adenylyl cyclase in both the olfactory bulb and mucosa, and document novel aspects of dopamine's physiological involvement in olfaction and of D2-mediated signal transduction.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Dopaminergic input is required for increases in serotonin output produced by behavioral activation: an in vivo microdialysis study in rat forebrain.

Previous research has demonstrated that pharmacological stimulation of postsynaptic dopamine D2 receptors produces increases in serotonin output. The present study explored whether this relationship also holds under physiological conditions. Accordingly, we examined the effects of D2 receptor blockade or unilateral dopamine depletion on behaviorally induced increases in extracellular serotonin levels in the corpus striatum and prefrontal cortex of freely moving rats using in vivo microdialysis. Extracellular levels of dopamine and serotonin, as well as behavioral activity, were increased by both mild tail pinch and the light-dark transition. Tail pinch-induced increases in serotonin levels (39+/-3% and 53+/-5% in the corpus striatum and prefrontal cortex, respectively), but not the accompanying behavioral changes, were blocked by local application of the D2 receptor antagonist raclopride (10 microM). D2 receptor blockade also disrupted the positive relationship between striatal serotonin levels and behavioral activity of animals across the light-dark transition (r=0.93 without raclopride, r=0.24 in presence of raclopride). Unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system also abolished increases in striatal serotonin output induced by both tail pinch and light-dark transition. A negative correlation was observed between the degree of striatal dopamine depletion and tail pinch-induced increases in serotonin efflux (r= - 0.88). Thus, both a local blockade of postsynaptic D2 receptors and striatal dopamine depletion prevented increases in serotonin output that normally accompany behavioral activation. These data indicate that the increases in the forebrain serotonin output produced by two distinct physiological/environmental manipulations appear to be largely dependent upon intact local dopaminergic neurotransmission.

Animals↗
PubMed1979

Acute poisoning from over-the-counter sleep preparations.

All cases received by the Rocky Mountain Poison Center involving over-the-counter (OTC) sleep preparations were studied during an 18-month period to elucidate 1) the range of toxicity; 2) characteristic symptoms, and 3) the time of onset of symptoms. In 155 cases reviewed retrospectively, the three most commonly ingested agents were Sominex, Nytol and Sleepeze. Multiple ingestions were also involved. Symptomatology was equally divided among no symptoms, mild symptoms and possible life-threatening symptoms. The least amount taken to produce possible life-threatening symptoms was 16 Sominex, 18 Nytol and 15 Sleepeze, although the average amount producing the same symptoms was approximately twice that. These symptoms were seen within six hours in all but three of the 39 cases presenting with these symptoms. There were no deaths.

Adolescent↗
PubMed2000

Chiral analysis of selected dopamine receptor antagonists in serum using capillary electrophoresis with cyclodextrin additives.

Dopamine D-2 receptor antagonists' eticlopride and sulpiride were determined in serum using capillary electrophoresis with cyclodextrin additives. Chiral resolution of S(-) and R(+) sulpiride and eticlopride were achieved using 2% sulfated-beta-cyclodextrin (S-beta-CD) in 20 mM citrate run buffer (pH 2.90). A 72-cm fused silica capillary operated in the reversed polarity mode voltage of 20 kV was used for the analysis. The analytes of interest were isolated from serum using a solid phase extraction procedure with recoveries in excess of 85% for all four enantiomers. The D-2 receptor antagonist (-) butaclamol was used as internal standard. The limits of detection were 0.3 and 0.1 microg/ml for S(-) and R(+) eticlopride and for S(-) and R(+) sulpiride, respectively, in 1 ml of serum. The limits of quantitation were 2 and 1 microg/ml for S(-) and R(+) eticlopride, and for S(-) and R(+) sulpiride, respectively. Calibration curves were linear over the 2-20 micro/ml range for eticlopride and 1-20 microg/ml range for sulpiride. The coefficients of determination were greater than 0.99 (n = 12 for eticlopride and n = 15 for sulpiride). Precision and accuracy of the method were 0.27-6.38 and 0.20-3.60% for S(-) eticlopride, 2.33-4.28 and 0.80-5.73%, for R(+) eticlopride, 3.46-6.84 and 0.80-4.26%, for S(-) sulpiride; and 4.71 -6.47 and 2.00-6.67%, for R(+)-sulpiride, respectively.

Buffers↗
PubMed2003

Diphenhydramine-induced wide complex dysrhythmia responds to treatment with sodium bicarbonate.

Diphenhydramine, a common ingredient in over-the-counter medications, is often taken in overdose. Toxicity is usually limited to anticholinergic symptoms. However, because diphenhydramine also exhibits type IA sodium channel blockade, cardiac toxicity is also possible. Although it would be expected that, like other type IA toxicities, diphenhydramine-induced cardiotoxicity could be responsive to hypertonic sodium bicarbonate, this finding is largely unappreciated. We describe 3 cases of diphenhydramine-induced cardiac toxicity that were responsive to bicarbonate.

Acetaminophen↗