Characterization of monoamine release in the lateral hypothalamus of awake, freely moving rats using in vivo microdialysis

Matos, F. Fátima; Rollema, Hans; Basbaum, Allan I.

doi:10.1016/0006-8993(90)90192-e

Cited by 39 publications

(31 citation statements)

References 34 publications

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“…The previous observation that the serotonin release induced by fenfluramine is prevented by pretreatment with reuptake inhibitors (Sabol et al 1992b) has led to the hypothesis that fenfluramine, in an amphetamine-like manner (Butcher et al 1988), causes serotonin release by reversing the transport mechanism normally removing the transmitter from the synaptic cleft; the present data indicate that mCPP has a similar mode of action. The concept that mCPPinduced serotonin release is not dependent upon exocytosis lends further support from the finding that it was not modified by co-administration of the sodium channel blocker TTX; similarly, fenfluramine-and amphetamine-induced serotonin release is not affected by TTX (Carboni and Di Chiara 1989;Matos et al 1990). …”

Section: Discussionmentioning

confidence: 73%

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Eriksson

Engberg²,

Bing³

et al. 1999

Neuropsychopharmacology

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Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5 mg/kg) induced a marked and doserelated increase in extracellular concentrations of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH) strain. Indicating that the effect of mCPP was caused by a reversal of the serotonin transporter, it was antagonized by pretreatment with the serotonin re-uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration of the sodium channel blocker tetrodotoxin (TTX; 1 m). mCPP was also shown to induce an increase in extracellular concentrations of dopamine in the nucleus accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the Sprague-Dawley (SD) Dopamine, In vivo microdialysis; Hippocampus; Striatum, Nucleus accumbens; Citalopram; Rat m-Chloro-phenylpiperazine (mCPP), the metabolite of the antidepressant drug trazodone, has recently gained marked attention as a putative probe of serotonergic function in clinical psychiatric research. Thus, the prolactin, ACTH, and cortisol responses to mCPP frequently have been used as putative markers of postsynaptic serotonin receptor function in various psychiatric disorders. Moreover, administration of mCPP has been shown to elicit, and/or aggravate, anxiety attacks in patients with panic disorder, obsessions in patients with obsessive compulsive disorder (OCD), elation in alcoholics and cocaine addicts, and positive symptoms in schizophrenic patients (see Murphy et al. 1991;Kahn and Wetzler 1991;Krystal et al. 1993;Buydens-Branchey et al. 1993;Krystal et al. 1994).mCPP displays high affinity to 5-HT2C receptors and moderate, or low, affinity to 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT3 receptors; in addition, the compound has some affinity for alpha-2-adrenoceptors. At the 5-HT2C receptor, mCPP seems to act as a partial agonist with relatively high intrinsic efficacy, whereas, at the other serotonin receptors, the intrinsic efficacy of mCPP is moderate or low (see Murphy et al. 1991 NO . 3 and Wetzler 1991). The behavioral and endocrine effects of mCPP observed in clinical studies are generally attributed to the direct effects of mCPP on various subtypes of serotonin receptors; in contrast, little attention has been paid to the report by Baumann et al. (1993) suggesting that mCPP may also stimulate serotonin release by means of an interaction with the serotonin transporter (see also Baumann et al. 1995).To further elucidate the possible influence of mCPP on the release of serotonin, we studied the effects of a high dose of mCPP on extracellular, hippocampal concentrations of serotonin in awake, freely moving rats using in vivo microdialysis.Enhanced dopaminergic neurotransmission has been suggested as a mechanism of importance both for the positive symptoms of schizophrenia and for the euphoria induced by such central stimulants as cocaine. The observations that mCPP may aggravate psychotic symptoms in schizophr...

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Section: Discussionmentioning

confidence: 73%

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Eriksson

Engberg²,

Bing³

et al. 1999

Neuropsychopharmacology

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“…In any event, phentermine has already been shown to be essentially inactive as a 5HT uptake inhibitor in vitro 14,17 (IC 50 ¼ 11 -14 mM). As for alternative mechanisms, although inhibition of monoamine oxidase (MAO) can yield relatively rapid elevations of extracellular 5HT, 18 these are usually persistent and can continue to rise for up to 5 h. 18,19 Again, however, phentermine has been shown to be extremely weak as an inhibitor of MAO A (IC 50 ¼ 100 -200 mM) 20,21 or MAO B (IC 50 ¼ 300 -900 mM). 20,21 Thus, the route by which phentermine evokes increases in extracellular 5HT in vivo is unclear.…”

Section: Discussionmentioning

confidence: 99%

Additive effects on rat brain 5HT release of combining phentermine with dexfenfluramine

et al. 2001

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OBJECTIVE AND DESIGN:This study examined the effects of the anti-obesity agents, phentermine and dexfenfluramine given alone or in combination, on in vitro and in vivo 5HT release from rat brain tissue. RESULTS: In vitro, phentermine was without effect on basal [ 3 H]5HT efflux from hypothalamic slices whereas dexfenfluramine (10 mM) evoked a 131% increase in [ 3 H]5HT release. In combination, the two drugs did not alter [ 3 H]5HT release beyond that caused by dexfenfluramine alone. At pharmacologically equivalent doses, phentermine (5.7 mg=kg, i.p.) caused a rapid, modest elevation, and dexfenfluramine (3 mg=kg, i.p.) a larger but equally rapid elevation of extracellular 5HT in the microdialysates from the rat anterior hypothalamus. In combination, the increase in extracellular 5HT evoked by these drugs was not significantly greater than the sum of their individual effects. CONCLUSIONS: This study provides evidence that phentermine's actions are not restricted to catecholamine systems and indicates that combining phentermine with dexfenfluramine results in an additive increase in neuronal 5HT release.

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“…Although localized application of TTX reversibly re duces the spontaneous release of serotonin [30,32,43], there is considerable variability in the literature on the ef fect of this treatment on 5-HIAA release. For example, applicaton of TTX during the day has little effect on 5-HIAA release in the caudate putamen [30] and SCN (present study), but significantly reduces 5-HIAA in the lateral hypothalamus [43].…”

Section: Discussionmentioning

confidence: 99%

“…This uncertainty has arisen from limitations in the current in vivo methodology for resolv ing the release of extracellular serotonin within the SCN as well as from numerous pharmacological investigations indicating that 5-HIAA may be an unreliable indicator of serotonin release [29][30][31][32][33]43], Collectively, these studies have shown that when the release of serotonin is elevated by neuronal depolarization using agents such as KC1, 5-HIAA is reduced [30,43,44], Also, inhibition of spon taneous serotonin release using the sodium channel blocker TTX has little effect on 5-HIAA levels, and 5-HIAA is not significantly affected by direct application of serotonin reuptake inhibitors [30,32,43,44], Findings such as these have been taken as evidence that extracellu lar 5-HIAA levels reflect primarily the intraneuronal me tabolism of an unreleased pool of serotonin. Thus, the diurnal rhythm of 5-HIAA seen in the SCN may reflect alterations in the metabolism of unreleased serotonin (i.e.…”

Section: Discussionmentioning

confidence: 99%

Diurnal Variation in 5-Hydroxyindole-Acetic Acid Output in the Suprachiasmatic Region of the Siberian Hamster Assessed by in vivo Microdialysis: Evidence for Nocturnal Activation of Serotonin Release

Ww²,

Sa³

et al. 1992

Neuroendocrinology

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In vivo brain microdialysis was used to characterize the daily pattern of 5-hydroxyindole-acetic acid (5-HIAA) release in the region of the suprachiasmatic nuclei (SCN) in freely behaving male Siberian hamsters housed under 16L:8D. A marked diurnal variation in the concentration of extracellular 5-HIAA was apparent, with peak levels (147 ± 5% of the daily mean; p < 0.05) occurring 2-3 h after lights-off. Smaller nocturnal rises in extracellular 5-HIAA were observed in the posterior hypothalamus and preoptic area (128 ± 4 and 123 ± 8% of the daily mean, respectively; both p < 0.05 vs. average daytime levels). Tryptophan loading increased 5-HIAA in SCN microdialysates by 44 ± 6%, and this response was enhanced by localized perfusion with tetrodotoxin (TTX; 5 µM). Localized applications of KC1 (150 mil) or veratridine (100 µM) decreased 5-HIAA by 62 ± 5 or 49 ± 11%, respectively. The effect of KC1 was not significantly affected by specific calcium channel blockers. Perfusion with TTX markedly decreased SCN 5-HIAA during the dark phase, but had little effect during the light phase (42 ± 8 vs. 12 ± 5% suppression, respectively; p < 0.01). Addition of serotonin (3 µM) to the perfusate significantly stimulated 5-HIAA output. This treatment increased the release of 5-HIAA more during the dark than during the light phase (61 ± 8 vs. 25 ± 5%, respectively; p < 0.01). Taken together, these results are evidence that: (1) there is increased TTX-sensitive (synaptic) release of serotonin at night that could contribute to the nocturnal rise in the extracellular concentration of 5-HIAA in the SCN; (2) clearance (uptake and/or metabolism) of extracellular serotonin in the SCN is higher at night; (3) 5-HIAA release in the SCN of the Siberian hamster is similar to that reported for other areas of the brain in other species, and (4) variations in 5-HIAA may, under certain physiological conditions, reflect changes in the extracellular concentration of serotonin.

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Characterization of monoamine release in the lateral hypothalamus of awake, freely moving rats using in vivo microdialysis

Cited by 39 publications

References 34 publications

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Additive effects on rat brain 5HT release of combining phentermine with dexfenfluramine

Diurnal Variation in 5-Hydroxyindole-Acetic Acid Output in the Suprachiasmatic Region of the Siberian Hamster Assessed by in vivo Microdialysis: Evidence for Nocturnal Activation of Serotonin Release

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