Dopamine and 5-hydroxytryptamine actions on the cardiac ganglion of the lobster Homarus americanus

The cardioexcitor monoamines dopamine (DA) and 5-hydroxytryptamine (5HT) accelerate bursting by isolated cardiac ganglia of the lobster Homarusamericanus most effectively when they act on a region of the ganglionic trunk anterior to the small cells which have been considered the pacemakers of the system. 5HT may exert its acceleratory action by depolarizing cell processes. Neither the somata nor the spike-initiating zones of the small cells have to be directly exposed to 5HT or DA in order for acceleration to occur. When 5HT is applied selectively to the small cells bursts are prolonged, probably as a result of increases in the duration of the endogenous burst-organizing potentials (driver potentials) generated by these neurons. This action on the small cells can lead to prolonged and intensified bursts of the full ganglion during the onset of 5HT action when the whole ganglion is exposed to the monoamine. Neither DA nor 5HT has a direct effect on the characteristics of large cell (motorneuron) driver potentials. Accepted: 3 September 1997     

Monoamine pharmacology of the lobster cardiac ganglion

Monoamine agonists and antagonists were applied to the lobster cardiac ganglion in an attempt to clarify the different actions of 5-hydroxytryptamine (5HT) and dopamine (DA) on this rhythmic pattern generator. Experiments were designed to determine whether the similar responses to 5HT and DA applied to the anterior region of the ganglion could be separated by pharmacological approaches, and whether the different responses to 5HT applied to the anterior and posterior regions of the ganglion could be attributed to mediation by different receptors. A small number of the 5HT agonists which were tested mimic the effects of 5HT, in that they increase the frequency of bursting and decrease burst duration when applied to the whole ganglion, but decrease burst frequency and increase burst duration when applied only to the posterior half. Other 5HT agonists decrease frequency and prolong bursts when applied to the whole ganglion. Of the DA agonists tested, none acts as DA itself does. Rather, they mimic the effects of 5HT applied to the posterior ganglion, by slowing bursting and prolonging bursts. The actions of agonists do not correspond in any clear way to the receptor specificities as defined in vertebrates. Most antagonists tested do not show similar specificities to their effects in vertebrates. In particular, most of the DA antagonists tested are more effective in blocking exogenous 5HT than DA. One monoamine agonist directly alters the properties of endogenous burst-organizing potentials (driver potentials) in the motorneurons of the ganglion.     

Amine modulation of the neurogenic Limulus heart

(1) The biogenic amines octopamine (OCT), dopamine (DA), epinephrine (E), and norepinephrine (NE) cause dose-dependent increases in both the rate and amplitude of contractions of the isolated Limulus heart-cardiac ganglion. Their relative ability to produce this excitation is OCT greater than DA approximately the same as E greater than NE. (2) The excitatory effects of all these amines are antagonized by the alpha-adrenergic blocker phentolamine and the dopaminergic antagonist haloperidol. The beta-adrenergic antagonist dichloroisoproterenol slightly reduces amine excitation, but is also a partial agonist. The beta-adrenergic antagonist propanolol, the alpha-blocker phenoxybenzamine, and the serotonin antagonist metergoline are ineffective. (3) In addition to their excitatory effects, DA and, to a lesser extent, NE initially reduce contraction rate and amplitude. (4) The transient inhibition is eliminated selectively by metergoline and is unaffected by the other antagonists. (5) The amines all increase the frequency of cardiac ganglion electrical bursting activity, whether ganglia are isolated or attached to cardiac muscle. Dopamine and NE also transiently inhibit the cardiac ganglion. (6) The amines do not alter myocardial resting tension, contractility, or membrane potential. (7) These amines appear to exert their modulatory effects on Limulus heart by altering the properties of the neurons which comprise its cardiac ganglion.     

Neurotensin interacts with dopaminergic neurons in rat brain

Neurotensin (NT) injected intracerebroventricularly in rat increases dopamine (DA) turnover in the corpus striatum and nucleus accumbens. Significant increases in 3,4-dihydroxyphenylacetic acid (DOPAC) levels occurred within 15 minutes after injection with peak levels at 60 minutes. The effect on NT on DOPAC and homovanillic acid (HVA) accumulation was dose-dependent at 3–100 μg. NT, like haloperidol, stimulated 3,4-dihydroxyphenylalanine (DOPA) accumulation in striatal neurons, in the presence of DOPA decarboxylase inhibitor, after injection of gamma-butyrolactone (GBL). NT had a similar stimulatory effect on DOPA levels in the accumbens while haloperidol (0.25 mg·kg^?1) had no significant effect in this brain region. NT did not block the inhibitory effect of apomorphine on DOPA accumulation in both the striatum and accumbens, while haloperidol inhibited apomorphine effect in both regions. NT also failed to displace ³H-spiperone from DA receptors and the presence of NT in the binding assay did not alter the ability of DA to displace ³H-spiperone in either brain region. These experiments demonstrate that NT increases DA turnover in both the nigrostriatal and mesolimbic pathways.     

Determination of trace amounts of dopamine by flow‐injection analysis coupled with luminol–Ag(III) complex chemiluminescence detection

A novel flow injection analysis‐direct chemiluminescence (FI‐CL) method has been developed for determination of trace amounts of dopamine (DA) based on the enhancing effect of DA on the CL reaction of luminol with an Ag(III) complex in alkaline solution. Under optimum conditions, CL intensities are proportional to the concentration of DA in the range of 1.0 × 10^?10 to 4.0 × 10^?8 mol L^?1. The detection limit is 3.0 × 10^?11 mol L^?1 for DA (3s), with a relative standard deviation (n = 13) of 2.3% for 1.0 × 10^?8 mol L^?1 DA. This method has also been applied for the determination of DA in commercial pharmaceutical injection samples. On the basis of the CL spectra and the results of the free‐radical trapping experiment of this work, a reaction mechanism for this CL reaction is proposed and discussed. Copyright © 2010 John Wiley & Sons, Ltd.     

Evidence for a coupling between dopaminergic receptors and phospholipid methylation in mouse B lymphocytes

Dopamine stimulated and dopaminergic antagonist·inhibited the enzymic synthesis of phosphatidyl N-monomethyl, N,N-dimethyl ethanolamine and phosphatidylcholine in mouse B lymphocytes in the presence of L-methionine. This effect was dose-dependent, stereospecific and the stimulation by dopamine was inhibited by very low doses of haloperidol from 10^?12 M to 10^?9 M. The stimulation of phospholipid methylation provoked by dopamine was increased by GTP. At higher doses DA inhibited and haloperidol stimulated phospholipase A₂. DA did not change the CDP choline pathway. The incubation of mouse B lymphocytes with L-methionine unmasks cryptic dopaminergic receptors. This effect is dose-dependent and inhibited by SIBA an inhibitor of phospholipid methylation. In a similar manner the efflux of Ca²⁺ which is sensitive to the change in membrane viscosity was increased by DA. These findings indicate that the dopaminergic receptors of the mouse B lymphocytes are coupled with phospholipid methylation.     

Release of endogenous dopamine from tuberoinfundibular neurons

Release of endogenous dopamine (DA) from arcuate-periventricular nucleus-median eminence fragments has been analyzed in an $\text{in vitro}$ static incubation system.Exposure of these hypothalamic fragments to increasing concentrations of K⁺ ions produced a dose-dependent release of endogenous DA. The highest rate of K⁺-stimulated DA efflux occurred in the first 10 minutes, thereafter it progressively decline reaching prestimulated levels at 30 minutes. If two consecutive depolarizing stimuli of 40 mM KCl were applied to the same hypothalamic fragment, after a 40 minutes rest period, an equivalent release of endogenous DA occurred. Removal of Ca⁺⁺ ions from the incubation medium containing the Ca⁺⁺ chelator EGTA caused a decrease of basal DA efflux and completely prevented the K⁺-induced release of DA.Furthermore when verapamil, a blocker of Ca⁺⁺ entrance, was added to the incubation medium in a concentration of 50 μM, the K⁺-induced DA efflux was completely counteracted, whereas spontaneous release was unmodified.Finally nomifensine, a potent blocker of DA uptake, added $\text{in vitro}$ in a final concentration of 10 μM, significantly reinforced K⁺-induced release of endogenous DA. Since nomifensine did not modify basal DA release, this study confirmed its prevalent uptake blocking property rather than its releasing action on DA.     

Fighting and Stinging Responses are Affected by a Dopamine Receptor Blocker Flupenthixol in Honey Bee Virgin Queens

Fighting and aggression are important tasks for self-preservation in animals. In honey bees, virgin queens fight against each other for survival in a monogynous colony. Because the virgin queens have higher levels of dopamine (DA) in the brain than do mated queens with low aggressiveness, DA may promote fighting and aggression behaviours of virgin queens. In the present study, we investigated the effect of DA on the fighting and stinging response of honey bee virgin queens. We injected two concentrations (10^?3 M and 10^?2 M) of DA and the DA receptor blocker flupenthixol into the abdomen of one-day-old virgin queens and observed fighting and stinging responses. DA injection did not affect fighting and stinging. Injections of 10^?3 M flupenthixol decreased the winning rate significantly, whereas 10^?2 M flupenthixol increased the winning rate, indicating the opposite effects on fighting responses depending on the degrees of blockade of DA signalling. In terms of the stinging response, 10^?2 M flupenthixol-injected virgin queens stung significantly more often than control and 10^?3 M flupenthixol-injected virgin queens. These results suggest an involvement of DA signalling in the regulation of fighting and aggression in virgin queens, although a blockade of DA does not always inhibit these behaviours.     

Pharmacological characterization of the dopamine-mediated accumulation of cyclic AMP in intact retina of rabbit.

Exposure of intact retinae of rabbit to dopamine, epinephrine and norepinephrine led to dose-related accumulations of cyclic AMP. Dopamine appears to be more potent than the two other catecholamines, since at 10^?6M it still induced a significant increase in cyclic AMP, whereas the two latter drugs were ineffective. Pure α- or β-adrenergic agonists such as phenylephrine or isoproterenol, as well as other drugs such as clonidine, DPI, (+)- and (±)-amphetamine, used at 10^?4M, were also devoid of agonist activity. In contrast a dopamine-analogue (epinine) and a dopamine-like drug (apomorphine) were as potent as dopamine. Blockade of the dopamine- or norepinephrine-elicited accumulation of cyclic AMP was achieved by antipsychotics such as fluphenazine, (+)-butaclamol and lithium, whereas propranolol (a β-adrenergic antagonist), phentolamine (an α-adrenergic antagonist) and (?)-butaclamol (an inactive compound), at 10^?4 to 5 × 10^?4M concentrations, showed no antagonist activity. The results indicate that the cyclic AMP production induced by catecholamines in intact retina of rabbit is a result of an activation of relatively pure dopamine receptors.     

Neural control of olfaction and tentacle movements by serotonin and dopamine in terrestrial snail

We investigated the role of serotonin (5HT) and dopamine (DA) in the regulation of olfactory system function and odor-evoked tentacle movements in the snail Helix. Preparations of the posterior tentacle (including sensory pad, tentacular ganglion and olfactory nerve) or central ganglia with attached posterior tentacles were exposed to cineole odorant and the evoked responses were affected by prior application of 5HT or DA or their precursors 5-hydroxytryptophan (5HTP) and l-DOPA, respectively. 5HT applications decreased cineole-evoked responses recorded in the olfactory nerve and hyperpolarized the identified tentacle retractor muscle motoneuron MtC3, while DA applications led to the opposite changes. 5HTP and l-DOPA modified MtC3 activity comparable to 5HT and DA action. DA was also found to decrease the amplitude of spontaneous local field potential oscillations in the procerebrum, a central olfactory structure. In vivo studies demonstrated that injection of 5HTP in freely moving snails reduced the tentacle withdrawal response to aversive ethyl acetate odorant, whereas the injection of l-DOPA increased responses to “neutral” cineole and aversive ethyl acetate odorants. Our data suggest that 5HT and DA affect the peripheral (sensory epithelium and tentacular ganglion), the central (procerebrum), and the single motor neuron (withdrawal motoneuron MtC3) level of the snail’s nervous system.     

Effects of the cilioexcitatory neurohumors dopamine and 5-hydroxytryptamine on cyclic AMP levels in the gill of the mussel Mytilus edulis.

Cyclic 3′, 5′-adenosine monophosphate (cAMP) has been identified in the ciliated gill epithelium of the marine mussel $\text{Mytilus}$$\text{edulis}$. In concentrations which stimulate the rate of particle transport by frontal gill cilia, DA and 5HT stimulate levels of cAMP within the gill. The stimulation occurs in as early as 15 sec and is graded from 10^?6M to 10^?4M. DA plus 5HT is not additive at maximal effective concentrations of both amines. ACH does not mimic the DA or 5HT stimulation of cAMP. Theophylline alone has a weak effect on cAMP levels; however, the effect of theophylline is potentiated in the presence of DA or 5HT. Dibutyryl cAMP produces a gradual stimulation in the rate of particle transport. It is suggested that the dopaminergic and serotonergic excitatory control of particle transport by frontal gill cilia of $\text{Mytilus}$$\text{edulis}$ is mediated through a cAMP second messenger system.     

The effects of dopamine on temperature regulation in goldfish

Summary Microinjections of dopamine (DA) were made into specific forebrain loci in goldfish (Carassius auratus: 40–85 g) to study the involvement of DA in behavioral thermoregulation. Injections of 25, 50, 100 and 250 ng DA into the anterior aspect of the nucleus preopticus periventricularis (NPP) led to consistent, dose-dependent decreases in selected temperature was observed following injections of 5 or 10 ng DA. Injections of the control solution were without effect.Injections of DA into other forebrain loci, including the posterior half of the NPP, either had no thermoregulatory effect or had minor thermoregulatory effects which, in comparison to injections into the most effective sites, were inconsistent and required larger doses to obtain. The decrease in selected temperature following injections of 100 ng DA into the anterior NPP was blocked by haloperidol, a dopaminergic antagonist, but not by phentolamine, a noradrenergic antagonist. Injections of haloperidol alone resulted in a minor, but statistically significant, increase in selected temperature.The most sensitive DA sites lie caudal to the sites most sensitive to norepinephrine within the anterior NPP. DA acts on the dopaminergic receptors of central thermoregulatory neurons in the anterior NPP of goldfish. These receptors appear to mediate behavioral responses to excessively warm environments.Abbreviations DA dopamine - NE norepinephrine - NPP nucleus preopticus periventricularis - PBS phosphate buffer solution     

Dopamine receptor-coupled modulation of the K+-depolarized overflow of 3H-acetylcholine from rat striatal slices: alteration after chronic haloperidol and alpha-methyl-p-tyrosine pretreatment

The effect of dopamine on the K⁺-depolarized overflow of ³H-acetylcholine from rat striatal slices was investigated to determine whether drug-induced changes in neuronal sensitivity to dopamine might be manifested in changes in striatal cholinergic activity. Dopamine was found to produce a dose-dependent inhibition of the K⁺-evoked release of ³H-Ach. This inhibition could be blocked by prior exposure of the slices to haloperidol, a dopamine receptor blocker. Dopamine receptors localized on striatal cholinergic axon terminals and possibly postsynaptic dopamine receptors on cholinergic perikarya and dendrites may mediate the DA inhibition of ³H-Ach release induced by high K⁺. Chronic pretreatment with haloperidol followed by alpha-methyl-p-tyrosine resulted in a significant shift to the left in the dose-dependent inhibition of K⁺-stimulated overflow of ³H-Ach by dopamine. This shift to the left in the dose-response curve may be the result of an increase in the number of striatal dopamine receptors produced by chronic dopamine receptor blockade and inhibition of dopamine synthesis.     

Interleukin-2 Modulates Evoked Release of [3H]Dopamine in Rat Cultured Mesencephalic Cells

Abstract: Mesencephalic cell cultures were used as a model to investigate the effects of interleukin-2 (IL-2) on evoked release of [³H]dopamine ([³H]DA) and γ-[³H]-aminobutyric acid ([³H]GABA). At low concentrations (10^?13-10^?12M), IL-2 potentiated [³H]DA release evoked by the excitatory amino acids N-methyl-D-aspartate (NMDA) and kainate, whereas higher IL-2 concentrations (10^?9-10^?8M) had no effect. IL-2 (10^?14-10^?8M) modulated K⁺-evoked [³H]DA release in a biphasic manner, with low concentrations (10^?12-10^?11M) of IL-2 potentiating and higher concentrations (10^?9-10^?8M) inhibiting K⁺-induced [³H]DA release. IL-2 (10^?14-10^?8M) by itself failed to alter spontaneous [³H]DA release. The inhibition by IL-2 of K⁺-evoked [³H]DA release was reversible and not due to neurotoxicity, as preexposure to IL-2 (10^?8M) had no significant effect on the subsequent ability of dopaminergic cells to take up and to release [³H]DA. Under our experimental conditions, IL-2 (10^?8 M) did not alter Ca²⁺-independent [³H]GABA release evoked by either K⁺ or NMDA. The results of this study indicate that IL-2 is able to potentiate [³H]DA release evoked by a number of different stimuli, including K⁺ depolarization and activation of both NMDA and non-NMDA receptor subtypes in mesencephalic cell cultures. IL-2 is active at very low concentrations, a finding that indicates a potent effect of IL-2 on dopaminergic neurons and implicates a physiological role for this cytokine in the modulation of DA release.     

Dopaminergic mediation of reward produced by direct injection of enkephalin into the ventral tegmental area of the rat

A conditioned place preference paradigm was employed to demonstrate the rewarding property of unilateral injections of 200 ng (D-ala2)-met5-enkephalinamide into the ventral tegmental area of the rat brain. This effect was attenuated in a dose-related manner by systemic injections of the dopamine receptor blocker haloperidol. In addition, selective lesions of the ascending dopamine (DA) pathways ipsilateral to the injection site blocked the rewarding effect when DA levels were reduced by more than 90%. Similar lesions in the contralateral hemisphere had no influence on this behavior. These data suggest that forebrain DA pathways can mediate some of the rewarding properties of opioid drugs.     

Differing Neurotoxic Potencies of Methamphetamine, Mazindol, and Cocaine in Mesencephalic Cultures

Abstract: The potent reinforcing effects of methamphetamine and cocaine are thought to be mediated by their interactions with CNS dopamine neurons. Both stimulants share the ability to block dopamine uptake potently, and methamphetamine can release cytoplasmic dopamine as well. There is also abundant evidence demonstrating the neurotoxic effects of methamphetamine. There are, however, limited studies that attempt to discern the neurotoxic mechanisms of these agents. The purpose of the present study was to characterize and compare the chronic in vitro effects of methamphetamine, cocaine, and the dopamine uptake blocker, mazindol, on cultured fetal mesencephalic dopamine neurons. Our studies examined biochemical mechanisms to evaluate the contribution of reuptake blockade versus release of dopamine. Using a dispersed cell preparation of fetal mesencephalon, cultures were treated for 5 days with the three uptake blockers. Dopamine function was assessed by measuring high-affinity [³H]dopamine uptake and by examining cultures for the presence of tyrosine hydroxylase-immunopositive neurons. Nonspecific neurotoxicity was assessed by staining for neuron-specific enolase and measuring lactate dehydrogenase activity. The results indicate that repeated administration of high concentrations of methamphetamine (10^?4 and 10^?3M) caused a generalized neurotoxicity whereas the effects of 10^?5M methamphetamine appeared to be specific to dopamine cells. Likewise, treatment of the cultures with mazindol (10^?6M) resulted in reduced dopamine uptake while not significantly affecting neuron-specific enolase or tyrosine hydroxylase immunostaining. On the other hand, repeated exposure to cocaine (10^?5 and 10^?4M) did not alter dopaminergic function in these cultures. The different mechanisms of action of these stimulants may explain the differences in neurotoxic potency of these compounds. The results demonstrate that a tissue culture model of fetal mesencephalic dopamine neurons provides a useful tool for the study of dopamine uptake systems and neuronal function.     

On the mechanism by which dopamine inhibits prolactin release in the anterior pituitary

An $\text{in}$$\text{vitro}$ perfusion system was used to assess the effects of chloride channel blockers, dopamine (DA) receptor agonists and antagonists, and GABA receptor agonists and antagonists on prolactin release from the mouse anterior pituitary. Dopamine and muscimol inhibited prolactin release ($\text{IC}{}_{50}{}^1\text{= 6 × 10}{}^{\mathrm{?8}}\text{M and}\text{10}{}^{\mathrm{?5}}\text{M}$ respectively). The GABA receptor antagonist bicuculline blocked the inhibition of prolactin release by muscimol but not dopamine. The dopamine receptor antagonist chlorpromazine blocked the dopamine- but not muscimol-induced inhibition of prolactin release. Haloperidol, however, reversed both the muscimol and dopamine induced inhibition of prolactin release. Furthermore, the chloride channel blocker picrotoxinin blocked the inhibition of prolactin release elicited by both dopamine and muscimol. These later results suggest that the anterior pituitary dopamine receptor which mediates the inhibition of prolactin release may be coupled to a picrotoxinin sensitive chloride ionophore and that haloperidol may affect the function of both DA and GABA receptors in the anterior pituitary.     

The role of central aminergic neurons in the action of 20-hydroxyecdysone on neurosecretory cells of Rhodnius prolixus

The enhancement of electrical activity of the neurosecretory cells in the brain and corpus cardiacum of Rhodnius prolixus induced by 20-hydroxyecdysone has been used as a means of examining the role of aminergic neurons in this reflex. The response of the brain and corpus cardiacum from mated ovariectomized females to 20-hydroxyecdysone was blocked by phentolamine and phenoxybenzamine (α-aminergic receptor antagonists) but not by propranolol (a β-aminergic receptor antagonist). Preparations taken from ‘reserpinzed’ females failed to respond to 20-hydroxyecdysone. Dopamine at 10^?7 M was capable of mimicking 20-hydroxyecdysone in activating the neurosecretory system from mated ovariectomised females as well as from ‘reserpinized’ mated ovariectomised females. The response to dopamine was blocked by phentolamine. The neurosecretory system from virgin ovariectomized females failed to respond to 10^?7 or 10^?6 M dopamine, but was activated by 10^?5 M dopamine.It is concluded that the action of 20-hydroxyecdysone onto the neurosecretory cells is indirect and involves aminergic interneurons. The results also suggest that the mating stimuli may function by enhancing the response of neurons to amines.     

Effects of des-tyr1 -γ-endorphin on dopamine release from various rat brain regions in vitro

In rat striatum, nucleus accumbens and frontal cortex slices 6×10^?8M of the potential neuroleptic peptide des-Tyr-γ-endorphin (DTγE) did not affect basal dopamine release but depressed K⁺-evoked release. Haloperidol at 5×10^?6M increased both basal and K⁺-induced release in striatal and nucleus accumbens slices whereas it increased only basal dopamine release in frontal cortex slices. At 5×10^?8M haloperidol, however, had no effect. It is concluded that DTγE may decrease dopaminergic activity in the brain by depressing depolarization-induced dopamine release, possibly via a presynaptic mechanism.     

Mechanism for amine modulation of the neurogenic Limulus heart: evidence for involvement of cAMP

The role of cyclic nucleotides as intracellular second messengers mediating the excitatory chronotropic and inotropic actions of octopamine (OCT) and dopamine (DA) on the neurogenic Limulus heart was investigated. Tissue levels of cAMP, but not cGMP, were significantly increased in isolated cardiac ganglia and cardiac muscle following 10 min exposure to 10(-5) M OCT or 10(-5) M DA. In both tissues, OCT elicited larger increases in cAMP than did DA. Amine-induced cAMP accumulation in the cardiac ganglion and in the cardiac muscle was prevented by the alpha-adrenergic blocker phentolamine. The adenylate cyclase activator forskolin and the phosphodiesterase inhibitor IBMX produced amine-like chronotropic and inotropic effects when applied to the isolated heart preparation. However, the kinetics of the responses differed for the two agents. Additional pharmacological agents (RO-20-1724, papaverine, SQ 20,009, and 8-parachloro-phenylthio cAMP) also had amine-like effects but to a lesser extent. The chronotropic, but not inotropic, effects of OCT and DA were potentiated in the presence of IBMX. These data suggest that a cAMP-dependent mechanism underlies the excitatory effects of the neuromodulators OCT and DA on the Limulus heart.