5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes

Sarhan, Hala; Cloëz‐Tayarani, Isabelle; Massot, O.; Fillion, Marie‐Paule; Fillion, G.

doi:10.1007/pl00005321

Cited by 51 publications

(21 citation statements)

References 37 publications

(52 reference statements)

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“…The synaptosomal preparation was obtained as described before (Sarhan et al 1999). Briefly, adult male rats, Wistar strain (Iffa Credo, l'Arbresle, France), weighing 160-200 g were sacrificed by decapitation.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we demonstrated that 5-HT 1B heteroreceptors located on dopaminergic terminals in rat striatum, modulate the release of dopamine by inhibiting the K + -evoked overflow of [ 3 H]-DA from synaptosomes (Sarhan et al 1999). However, the functional potency of the rodent selective 5-HT 1B receptor agonist (CP93,129) to elicit this response was low (EC 50 =1.8 µM) compared to its potency to inhibit the adenylate cyclase in rat cortex (EC 50 =56 nM, Macor et al 1991), and to inhibit the K + -evoked [ 3 H]-5HT overflow from synaptosomes of rat hippocampus (EC 50 = 27 nM, Bolaños-Jiménez et al 1995).…”

Section: Introductionmentioning

confidence: 99%

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Differential sensitivity of 5-HT1B auto and heteroreceptors

Sarhan

Fillion

1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The effect of the native and rodent-selective 5-HT1B receptor agonists (5-hydroxytryptamine (5-HT) and CP93,129) on the K+-evoked overflows of [3H]5-HT, [3H]dopamine (DA) and [3H]acetylcholine (ACh) was studied in synaptosome preparations obtained from rat brain striatum or hippocampus loaded with radiolabeled neurotransmitter. The aim of the study was to compare the different potencies of the specific 5-HT1B receptor agonists to stimulate the auto and heteroreceptors and to modulate the different neurotransmitter release. Results show that under the same experimental conditions, 5-HT and CP93,129 exhibited significantly higher potencies in inhibiting the K+-evoked overflow of [3H]5-HT from synaptosomes of rat striatum (IC50=2.0+/-1.8 nM and 20.5+/-3.1 nM, respectively) than in inhibiting the K+-evoked overflow of [3H]DA from synaptosomes of the same cerebral region (IC50= 0.8+/-0.2 microM and 1.8+/-0.4 microM, respectively), or [3H]ACh from synaptosomes of hippocampus (IC50=1.7+/-0.8 microM for CP93,129). The inhibitory effects of the 5-HT1B receptor agonists on [3H] K+-overflows were antagonized by the selective 5-HT1B receptor antagonist (SB224289), further indicating that the observed effects were 5-HT1B receptor specific. Sumatriptan, a selective r5-HT1D receptor agonist, did not show any significant effect on the K+-overflow of [3H]5-HT in the range of concentrations (10(-10) to 10(-6) M), and did not affect the K+ overflow of [3H]DA or [3H]ACh at concentrations (10(-9) to 10(-4) M), which exclude the involvement of 5-HT1D receptors. These inhibitory effects of the 5-HT1B receptor agonists were highly attenuated by pertussis toxin in the three systems studied, suggesting the involvement of Gi/Go-proteins in the transduction mechanism pathway of the receptor generated signal. In conclusion, these results suggest that 5-HT1B heteroreceptors located on dopaminergic and cholinergic terminals exhibit a lower sensitivity to 5-HT1B receptor agonist and antagonist than do 5-HT1B autoreceptors. The observed difference in functional sensitivities of 5-HT1B auto- and heteroreceptors may represent important consequences in the physiological control of the release of serotonin versus that of other neurotransmitters.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential sensitivity of 5-HT1B auto and heteroreceptors

Sarhan

Fillion

1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Work in striatal synaptosomes, however, suggests an inhibitory role for these receptors (Sarhan et al 1999(Sarhan et al , 2000. It is possible that an overall facilitation overshadows this inhibitory effect in vivo but requires feedback to the SN and is therefore not observed in synaptosomes.…”

Section: Nigrostriatal Pathwaymentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

526

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…Building on the evidence that 5-HT1B receptors mediate motor activity as seen in the knock-out mice studies, it is also recognized that serotonin's regulatory control over dopamine neurotransmission is mediated in part by the 5-HT1B receptors. For example, Sarhan and colleagues demonstrated that 5-HT1B heteroreceptors played an inhibitory role in dopamine release in rat striatum, 17 whereas other studies have demonstrated that 5-HT1B receptors facilitate DA release in rat striatum, 18 nucleus accumbens 19 and prefrontal cortex. 20 Because serotonin modulates dopamine activity through its various receptors including 5-HT1B, these receptors can have an influence on dopaminemediated behaviours, relevant to those seen in children with ADHD.…”

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confidence: 99%