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M P Galloway

Publications and source records attributed to M P Galloway.

At least 19 recordsLinked to original sources
PubMed1998

Nitric oxide and potassium chloride-facilitated striatal dopamine efflux in vivo: role of calcium-dependent release mechanisms.

Previous studies investigating the calcium-dependency of nitric oxide-facilitated striatal dopamine efflux have produced conflicting results. In the current study, we have investigated the role of extracellular calcium in nitric oxide and potassium chloride-evoked striatal dopamine efflux in vivo using microdialysis. Dialysis probes were implanted in the anterior dorsal striatum of chloral hydrate-anesthetized rats. Intrastriatal infusion (20 min fraction) of the nitric oxide generators sodium nitroprusside (200 microM, 500 microM, or 1 mM) and 3-morpholinosydnonimine (1 mM) increased extracellular dopamine levels. The facilitatory effects of 3-morpholinosydnonimine and potassium chloride on dopamine efflux were attenuated following pretreatment (100 min) and co-infusion of calcium free artificial cerebral spinal fluid containing magnesium chloride. Local potassium chloride infusion (100 mM) administered alone elevated striatal dopamine efflux to a similar degree as potassium chloride (100 mM) delivered 60 min after 3-morpholinosydnonimine infusion. These results demonstrate that like potassium chloride, nitric oxide facilitates striatal dopamine efflux in vivo via a mechanism largely dependent on extracellular calcium. Also, as intrastriatal potassium chloride infusion evoked similar increases in extracellular dopamine levels in controls and subjects receiving pretreatment with the NO-generator 3-morpholinosydnonimine, it is unlikely that the functional integrity of DA nerve terminals is compromised via a neurotoxic disruption of plasma membrane potential following enhanced striatal NO production.

Animals↗
PubMed1997

Inhibition of glutamate reuptake potentiates endogenous nitric oxide-facilitated dopamine efflux in the rat striatum: an in vivo microdialysis study.

The current study investigated the effects of the nitric oxide synthase (NOS) substrate, N(G)-hydroxy-L-arginine (H-ARG) and the selective glutamate (GLU) reuptake inhibitor (2S)-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) on striatal dopamine (DA) and glutamate (GLU) efflux in vivo. Concentric microdialysis probes were stereotaxically implanted in the anterior-medial striatum of chloral hydrate-anesthetized rats. Intra-striatal infusion of PDC (200 microM) elevated extracellular (EC) DA and GLU levels concurrently over a 10 fraction collecting period without affecting EC asparagine levels. Infusion of H-ARG (200 microM) for six 20-min fractions, also significantly elevated EC DA levels. In the presence of PDC (200 microM), co-perfusion of H-ARG (200 microM) resulted in supra-additive increases in EC DA levels. The synergistic effect of PDC and H-ARG infusion on DA efflux was attenuated by co-infusion of the NOS inhibitor, 7-nitroindazole (100-200 microM). These results suggest that while both endogenous NO and GLU regulate striatal DA efflux via facilitatory influences, enhanced glutamatergic tone on striatal NOS-containing neurons may potentiate NO-synthesis and subsequently NO-induced DA efflux.

Animals↗
PubMed1997

Interactions between cocaine and (-)-DS 121: studies with 2-deoxyglucose autoradiography and microdialysis in the rat brain.

(-)-DS 121 [S-(-)-3-(3-cyanophenyl)-N-n-propyl piperidine], a dopamine autoreceptor preferring antagonist, has been shown to stimulate locomotor activity and induce conditioned place preference. However, the drug fails to facilitate intracranial self-stimulation or substitute for cocaine in cueing experiments, and it blocks cocaine self-administration. In the present study using 2-deoxyglucose autoradiography, (-)-DS 121 (at 50 but not 15 mg/kg i.p.) significantly and selectively increased local cerebral glucose utilization in the olfactory cortex, medial and lateral septum, hippocampal areas, substantia nigra pars reticulata, caudate, and mammillary body. Local cerebral glucose utilization was depressed in caudal areas of the cortex. Interestingly, however, both doses of (-)-DS 121 blocked the increases in local cerebral glucose utilization produced by 5 mg/kg i.v. cocaine. The present study also evaluated the effects of (-)-DS 121 of extracellular striatal dopamine levels using microdialysis in freely moving rats. By itself, 15 mg/kg of (-)-DS 121 increased extracellular striatal dopamine levels to approximately 300% of controls. Cocaine (5 mg/kg i.v.) produced a 370% increase in striatal dopamine levels. When rats were pretreated with (-)-DS 121, a subsequent dose of cocaine augmented the increase in extracellular striatal dopamine to 870% of controls. The results support the contention that (-)-DS 121 possesses weak cocaine-mimetic effects and that its antagonism of cocaine's subjective effects are due to interactions with dopamine at postsynaptic sites. It is hypothesized that, like other preferential autoreceptor antagonists, (-)-DS 121 may be useful as a pharmacotherapy in drug addiction.

Animals↗
PubMed1997

MDMA induced dopamine release in vivo: role of endogenous serotonin.

Acting as a substrate at the serotonin (5-HT) transporter, (+)-MDMA (3,4-methylenedioxymethamphetamine), is a potent releaser of 5-HT and causes toxicity to 5-HT neurons after repeated exposure. (+)-MDMA also releases dopamine (DA), although with less potency. Since we have shown previously that the intrastriatal application of 5-HT facilities DA release, it was hypothesized that increased release of striatal 5-HT after MDMA may influence extracellular levels of DA. Using microdialysis in vivo, we found that (+)-MDMA (4.7 mumol/kg, i.v.) administration increased extracellular striatal DA levels to 501% of control (p < 0.01, n = 12). However, in the presence of fluoxetine (14.4 mumol/kg, s.c.), which prevents (+)-MDMA effects on 5-HT release, the (+)-MDMA-induced increase in DA was significantly less (to 375% of control, p < 0.05, vs. no fluoxetine, n = 8). In vitro studies with striatal slices, to test drug selectivity, showed that (+)-MDMA (0.3-3 microM) increased extracellular levels of both DA and 5-HT in a dose-dependent manner. Fluoxetine (3 microM) completely blocked the effects of (+)-MDMA on 5-HT release, but did not alter (+)-MDMA-induced DA release in vitro. The selective DA transport inhibitor GBR-12909 (1 microM), blocked (+)-MDMA's effect on DA release. It is concluded that 5-HT release after (+)-MDMA treatment partially contributes to (+)-MDMA's effect on DA release in vivo.

Animals↗
PubMed1996

Repeated cocaine exposure attenuates the ability of 5-hydroxytryptamine to release striatal dopamine in vivo.

Cocaine was administered repeatedly to rats and striatal microdialysis performed 1, 7, 14, or 21 days after the last cocaine injection. Local perfusion of 10 microM serotonin (5-hydroxytryptamine, 5-HT) increased basal dopamine levels approximately 7-fold (664 +/- 79%, 813 +/- 104% and 669 +/- 22%, n = 6, P < 0.0001) in saline-treated controls, whereas in cocaine-treated animals the effect was significantly attenuated (432 +/- 55%, 465 +/- 61% and 497 +/- 48% n = 6-10, P < 0.03) at 1, 7 and 14 days of withdrawal. The 5-HT effect on dopamine release returned to control levels 21 days after cocaine exposure and was not altered by acute cocaine treatment (30 mg/kg, i.p. 24 h prior). The results suggest that repeated cocaine administration attenuates the effectiveness of 5-HT on striatal dopaminergic activity.

Animals↗
PubMed1996

Dopamine autoreceptor reserve in vitro: possible role of dopamine D3 receptors.

Receptor alkylation in vivo with N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) decreased the potency, but not the efficacy, of the dopamine D3 receptor-preferring agonist 7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OH-DPAT) at synthesis modulating dopamine autoreceptors in striatal and olfactory tubercle slices stimulated by 30 mM K+. In contrast, 7-OH-DPAT was ineffective in slices exposed to forskolin (10 microM). The results support the presence of autoreceptor reserve in vitro, and the partial involvement of dopamine D3 receptors in the autoregulation of dopamine synthesis.

Adenylyl Cyclases↗
PubMed1996

Desensitization of 5-hydroxytryptamine-facilitated dopamine release in vivo.

Desensitization to serotonin (5-hydroxytryptamine, 5-HT)-facilitated dopamine release in vivo develops following either continuous or repeated pulses of 5-HT. For instance, an initial 20 min pulse of 5-HT (10 microM) produced a 715 +/- 150% increase in basal dopamine, an effect which steadily declined over 5 subsequent fractions to 222 +/- 80%. Also, secondary pulses (s2) of 5-HT administered 40 min following the primary pulse (s1), elicited a 327 +/- 16% increase in dopamine levels, significantly decreased from the primary s1 pulse. Augmentation of either protein kinase A or protein kinase C systems attenuated 5-HT-facilitated dopamine release, suggesting a role for protein kinases in regulating the desensitization process.

Animals↗
PubMed1996

Regulation of serotonin-facilitated dopamine release in vivo: the role of protein kinase A activating transduction mechanisms.

Recent neuroanatomical, biochemical, and electrophysiological studies suggest that serotonin (5HT) can modulate dopaminergic function at the level of the cell body and the nerve terminal. The receptor subtypes, regulatory processes, and intracellular transduction mechanisms mediating these interactions remain to be characterized. The potential involvement of cAMP in mediating 5HT-facilitated increases in extracellular levels of striatal dopamine (DA) was assessed using in vivo microdialysis. Local infusion of 0.4 nmol 5HT delivered via probes located in the anterior striata of chloral hydrate-anesthetized male rats significantly increased extracellular DA levels to approximately 700% of basal control levels. Local, intrastriatal infusion of either 2 nmol forskolin, 2 nmol rolipram, 100 nmol isobutylmethylxanthine, or 200 nmol dibutyryl cAMP significantly increased basal DA levels to 28 +/- 3%, 143 +/- 5%, 56 +/- 7%, and 52 +/- 3% above control levels, respectively. Additionally, coperfusion of any of these agents with 5HT significantly decreased the 5HT-facilitory effect on DA release to approximately 50% of observed 5HT controls. The current results suggest a role for the cAMP second-messenger systems in modulating 5HT-facilitated DA release.

Animals↗
PubMed1996

Intrastriatal infusion of (+/-)-S-nitroso-N-acetylpenicillamine releases vesicular dopamine via an ionotropic glutamate receptor-mediated mechanism: an in vivo microdialysis study in chloral hydrate-anesthetized rats.

The existence of both nitric oxide synthase (NOS) immunoreactive interneurons and amino acid neurotransmitter-mediated nitric oxide (NO) release in the striatum suggests a role for NO in modulating striatal function. To explore the potential interaction between NO and dopaminergic neurotransmission, the NO-releasing agent (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) was administered locally into the anterior medial striatum of chloral hydrate-anesthetized rats. SNAP, at 0.5, 1, and 2 mM concentrations, elevated striatal extracellular (EC) dopamine (DA) to 200 +/- 42, 472 +/- 120, and 2,084 +/- 496%, respectively, above baseline levels. Perfusion with (+/-)-penicillamine (PEN, 1 mM), the non-NO-containing carrier component of SNAP, was ineffective, indicating that PEN is not responsible for SNAP-mediated DA release. Additional microdialysis experiments suggest SNAP-mediated DA release is not due to NO-induced neurotoxicity or blockade of the DA transporter. The DA-releasing effect of SNAP was attenuated under calcium-free conditions and abolished in rats pretreated with reserpine (5 mg/kg), implicating a calcium-sensitive vesicular-dependent release process. To determine the mechanism of SNAP-mediated DA release, the guanylyl cyclase (GC) inhibitor LY 83583 (100 microM) was administered 100 min before and during the SNAP pulse. LY 83583 elevated EC DA levels approximately fivefold and potentiated the DA-releasing effect of SNAP to 2,598 +/- 551% above basal DA levels. Similar pretreatments with both the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 (10 microM) and the competitive NMDA-receptor antagonist (+/-)-3-(carboxypiperazin-4-yl) propyl-1-phosphonic acid [(+/-)-CPP, 100 microM] blocked SNAP-mediated DA release. SNAP-mediated DA release was also significantly blunted by pretreatment and coperfusion with MgSO4 (10 mM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM) but not (+)-2-amino-3-phosphonopropionic acid (AP-3, 10 microM). These results suggest that NO releases DA via a calcium-sensitive vesicular-dependent process that is independent of GC activation. In addition, NMDA and kainate/ (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated mechanisms are implicated in NO-induced DA release.

Anesthesia↗
PubMed1995

Evidence for 5-HT autoreceptor-mediated, nerve impulse-independent, control of 5-HT synthesis in the rat brain.

To gain further insight into the operation of 5-HT autoreceptor-mediated feedback control of 5-HT biosynthesis in serotonergic nerve terminal areas, the effect of the 5-HT1B and the 5-HT1A receptor agonists, TFMPP and 8-OH-DPAT, respectively, were investigated in the rat central nervous system (CNS) using in vivo and in vitro neurochemical approaches. TFMPP suppressed 5-HT synthesis (5-HTP accumulation after decarboxylase inhibition) both in vivo and in vitro. In vivo, the 5-HT synthesis-suppressing effect of the drug (3.0 mg/kg, s.c.) proved resistant to either acute hemitransection or reserpine (5 mg/kg, i.p.; 90 min before) pretreatment. In vitro, in cortical, hippocampal and striatal slice preparations, TFMPP (0.1-10 microM) decreased 5-HT synthesis under basal and stimulated (30 mM K+) conditions, an effect which was unaltered by prior in vivo reserpine-induced 5-HT depletion but was attenuated in the presence of 5-HT1B receptor antagonists such as methiothepin, cyanopindolol or propranolol. The 8-OH-DPAT (0.1 mg/kg, s.c.)-induced decrease of 5-HT synthesis in vivo was abolished by hemitransection but resistant to acute reserpine pretreatment; 8-OH-DPAT (10 microM) did not decrease 5-HT synthesis in vitro. In conclusion, the present study confirms the importance of 5-HT autoreceptors in the feedback control of nerve terminal 5-HT biosynthesis. Specifically, our data indicate: (1) that the reduction of rat brain 5-HT synthesis after TFMPP is mediated by 5-HT1B autoreceptors located on the serotonergic axon terminals, and (2) that the effect is directly mediated and occurs independently of 5-HT neuronal firing and intact monoamine stores.

Animals↗
PubMed1995

Dopamine D3-preferring ligands act at synthesis modulating autoreceptors.

Several compounds exist that demonstrate a binding preference for cloned dopamine D3 receptors vs. D2 receptors, including (+/-)7-OH DPAT, (+)-UH232 and (+)-AJ76. Inasmuch as recent evidence suggests that the dopamine D3 receptor may function as a dopamine autoreceptor, we have investigated the ability of these D3-preferring ligands to act at synthesis modulating dopamine autoreceptors using the gamma-butyro-lactone model in vivo to isolate the presynaptic effects of (+/-)7-OH DPAT, (+)-UH232 and (+)-AJ76. Further, given the discrete anatomical distribution of the D3 receptor, the striatum, n. Accumbens, and olfactory tubercles were examined for comparative analyses. (+/-)7-OH DPAT displayed agonist characteristics at synthesis modulating dopamine autoreceptors with a greater potency in the olfactory tubercle vs. either the striatum or the nucleus accumbens (ED-50 values were 31.8, 38.1 and 10.2 micrograms/kg for the striatum, nucleus accumbens and olfactory tubercles, respectively). Further, (+)-UH232 and (+)-AJ76 attenuated the effects of (+/-)7-OH DPAT (60 micrograms/kg s.c.) in all three regions examined. However, the effects of (+/-)7-OH DPAT were antagonized to a lesser extent in the olfactory tubercles than in either the striatum or the nucleus accumbens. Given the relative abundance of D3 receptors in the olfactory tubercles, the data are consistent with the notion that (+/-)7-OH DPAT may exert its autoreceptor effects preferentially through dopamine D3 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Biochemical and fluorodopa positron emission tomographic findings in an asymptomatic carrier of the gene for dopa-responsive dystonia.

We report cerebrospinal fluid monoamine metabolite analyses and 6-[18F]fluoro-1-dopa positron emission tomography (FD-PET) from an asymptomatic carrier of the gene for dopa-responsive dystonia. Cerebrospinal fluid homovanillic acid, tetrahydrobiopterin, and neopterin concentrations were reduced in this man and in his affected children. His FD-PET was normal, as we have previously found in dopa-responsive dystonia. Neurological function and FD-PET may be normal despite marked abnormality in dopamine metabolism.

Adolescent↗
PubMed1993

Plasma catecholamine levels during temperature biofeedback training in normal subjects.

Thirty-nine normal volunteers of both sexes were randomly assigned to receive 8 sessions of temperature biofeedback or autogenic training to increase finger temperature. Temperature biofeedback subjects produced significant elevations in finger temperature during training, whereas those who received autogenic training did not. Temperature feedback subjects had significantly higher heart rates and diastolic blood pressures during training compared to autogenic subjects. There were no significant changes or group differences in plasma catecholamine levels. These data do not support the hypothesis that feedback-induced vasodilation is accompanied by decreased sympathetic activation in normal populations, when only temperature biofeedback is employed.

Autogenic Training↗
PubMed1993

Serotonin-facilitated dopamine release in vivo: pharmacological characterization.

The receptor specificity of serotonin (5-HT) agonist-induced facilitation of dopamine (DA) release was assessed by using in vivo microdialysis. The 5-HT receptor selective agonists RU 24969 [5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate], 2-methylserotonin maleate, 5-methoxytryptamine HCl, 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl were perfused through probes located in the anterior lateral striata of chloral hydrate-anesthetized rats. The agonists increased extraneuronal levels of DA in a dose-dependent manner, suggesting receptor selectivity in the order of 5-HT1b > 5-HT4 >> 5-HT2 = 5-HT1a. Coperfusion of the 5-HT1 antagonist pindolol with RU 24969 reduced the efficacy of RU 24969. The 5-HT2 antagonist ritanserin (6-[2-[4[bis(4-fluorophenyl)methylene]-1-piperadinyl]- ethyl]-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one) did not antagonize the effect of either 5-HT or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl on DA levels. MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) and ICS 205930 (3-tropanyl-indole-3-carboxylate), both 5-HT3 antagonists, decreased the efficacy of 5-HT. The partial 5-HT4 antagonist ICS 205930 reduced DA released by perfusion of the 5-HT1/2/4 agonist 5-methoxytryptamine HCl. Coperfusion of antagonists with agonists indicated involvement of 5-HT1 and 5-HT3 receptors and a lack of involvement of 5-HT2 receptors in the 5-HT-induced facilitation of DA release. Determination of the role of 5-HT4 receptors will require additional work with more selective ligands.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Markers of dopamine metabolism in Parkinson's disease. The Parkinson Study Group.

We used two analytic methods (a multichannel coulometric electrode array with high-performance liquid chromatography, and gas chromatography-mass spectrophotometry) to measure CSF dopamine (DA) and its metabolites in mildly affected, unmedicated subjects with Parkinson's disease (PD). The mean (+/- SD) concentration of homovanillic acid (HVA), the most abundant product of DA turnover, was 164.57 +/- 95.05 nM. As sequential aliquots of CSF were collected from the first to 23rd ml, CSF HVA concentration almost doubled. After HVA, 3-O-methyldopa (3-O-MD) was the next most abundant compound. The summed concentrations of 3-O-MD, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, DA, DA-3-sulfate, homovanillol, and levodopa (LD) amounted to 12.6% of HVA. Concentrations of the DA metabolites did not correlate to a variety of indices of PD severity. The presence of LD and 3-O-MD may be indicators of DA synthesis and possibly could reflect compensatory processes among surviving dopaminergic neurons of the PD brain.

Aged↗
PubMed1992

Acute administration of amphetamine: differential regulation of dopamine synthesis in dopamine projection fields.

In order to study the inhibitory mechanisms regulating dopamine (DA) synthesis in vivo, the effect of amphetamine in the presence and absence of selective D1 and D2-DA receptor antagonists was examined in various brain regions. In response to amphetamine (3 mg/kg s.c.) administration, DA synthesis in the striatum, but not the nucleus accumbens or the medial prefrontal cortex, exhibited a biphasic response (increased followed by decreased). The D1 selective antagonist, SCH 23390 (0.5 mg/kg s.c., 60 min), modestly increased DA synthesis (30%) in the striatum but not in the nucleus accumbens or the prefrontal cortex. However, pretreatment with the D1 DA receptor antagonist did not prevent the amphetamine-induced elevation of striatal DA synthesis 45 min after amphetamine administration. The D2 selective antagonist, eticlopride (2 mg/kg s.c., 60 min), increased DA synthesis in both the striatum and the nucleus accumbens but not in the prefrontal cortex. Although amphetamine alone increased DA synthesis only in the striatum, in the presence of D2-DA receptor blockade, amphetamine increased DA synthesis in the striatum, the nucleus accumbens and the medial prefrontal cortex. The results support the hypothesis that DA synthesis is differentially regulated by distinct inhibitory mechanisms depending on the projection field. The apparent differences in regulatory mechanisms may allow selective alteration of DA synthesis in one particular projection field, while other areas remain unaffected.

Amphetamine↗
PubMed1991

Facilitation of dopamine release in vivo by serotonin agonists: studies with microdialysis.

Using microdialysis, changes in extraneuronal levels of dopamine (DA), and the metabolites of DA and serotonin (5-HT), were monitored concurrent with perfusion of 5-HT1 agonists into the anterior striata of anesthetized rats. Perfusion of 5-HT facilitated DA release in a dose dependent manner, and to a greater extent than any other agonist tested. Extraneuronal DA levels increased 34% with perfusion of 0.04 nmol 5-HT and 18-fold with perfusion of 4.0 nmol 5-HT. Perfusion with multiple doses of either 1-(m-chlorophenyl)piperazine (m-CPP) or trifluoromethylphenylpiperazine (TFMPP) also resulted in a dose-dependent facilitation of DA release with a 40% increase in extracellular DA produced by either 0.4 nmol m-CPP or 10.0 nmol TFMPP. A 50-fold increase in DA followed 40.0 nmol m-CPP, while 160 nmol TFMPP enhanced DA 11-fold. Local application of either 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate (RU24969) or 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (2.0 nmol perfused over 20 min) increased extracellular DA by 300 and 40%, respectively. RU24969 (2.0 nmol) also facilitated DA release following systemic pretreatment with 8-OH-DPAT (100 micrograms/kg). Perfusion with fenfluramine to release endogenous 5-HT also increased extraneuronal DA in a dose-dependent manner, and this facilitation was prevented by pretreatment with the 5-HT reuptake inhibitor fluoxetine. The facilitation of DA release by 0.4 nmol 5-HT was reduced by pretreatment with the 5-HT1 antagonist pindolol (4.0 nmol). These results suggest that serotonergic innervation of the anterior striatum may exert a facilitatory influence on DA release.

Animals↗