Acute administration of amitriptyline and mianserin increases dopamine release in the rat nucleus accumbens: possible involvement of serotonin 2C receptors

Matteo, Vincenzo Di; Mascio, Michele Di; Giovanni, Giuseppe Di; Esposito, Ennio

doi:10.1007/s002130000420

Cited by 56 publications

(24 citation statements)

References 41 publications

(42 reference statements)

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“…In the same experiment there were, however, no differences in the basal or evoked DA levels between chloral hydrate anesthetized and unanaesthetized rats [29]. Additional acute microdialysis studies examining accumbens DA have used choral hydrate as an anesthetic because it has minimal effects on mesoaccumbens DA efflux over time [30][31][32][33] and it has a long effective half life (∼6.5 h).…”

Section: Discussionmentioning

confidence: 99%

Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

Bello

Hajnal

2006

Physiology & Behavior

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Dopaminergic systems have been implicated in diabetes and obesity. Notwithstanding, the most basic relationship between dopamine and plasma insulin as well as glucose levels yet remains unknown. The present experiments were designed to investigate the effects of acute hyperinsulinemia on basal dopamine levels in the nucleus accumbens of the rat under chloral hydrate anesthesia using acute microdialysis in combination with the hyperinsulinemic-glycemic clamping procedure. In Experiment 1, each rat was infused with one of three concentrations of insulin (2.4, 4.8, or 9.6 mU/ kg per min) while plasma glucose levels were maintained at euglycemia (∼5.5 mmol/L). Dopamine, dihydroxyphenylacetic acid and homovanillic acid were not significantly different from baseline during either the clamp or post clamp periods for all insulin concentrations. In Experiment 2, rats were infused with the highest concentration of insulin (9.6 mU/kg per min) and plasma glucose levels were maintained at either hypoglycemia (∼3 mmol/L) or hyperglycemia (∼14 mmol/L). Dopamine was elevated at 100 min (+113% above basal levels) and 120 min (+117%) in the hypoglycemic condition and at 120 min (+121%) in the hyperglycemic condition. In the hyperglycemic post clamp period, homovanillic acid was decreased below basal levels (approximately -32%). These results together suggest that short-term blood glucose deviations coupled with acute hyperinsulinemia affect the mesoaccumbens dopamine system.

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Section: Discussionmentioning

confidence: 99%

Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

Bello

Hajnal

2006

Physiology & Behavior

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“…Furthermore, the 5-HT 2C agonist, Ro 60-0175, attenuates cocaine-primed reinstatement (Grottick et al, 2000), providing further evidence for a role of 5-HT 2C receptors in this behavior. SB 242,084 likely enhances cocaine-primed reinstatement by enhancing dopamine neurotransmission since previous research has shown that 5-HT 2C receptors inhibit mesocorticolimbic dopamine release , 2000a, which is thought to play a role in cocaine-primed reinstatement of cocaine-seeking behavior (Weissenborn et al, 1996;Khroyan et al, 2000;Alleweireldt et al, 2002). The reason for the discrepancy in the effects of SB 242,084 on cocaine reinstatement across studies is unclear, but may be due to differences in cocaine priming and/or SB 242,084 doses tested.…”

Section: Discussionmentioning

confidence: 99%

Differential Roles of 5-HT Receptor Subtypes in Cue and Cocaine Reinstatement of Cocaine-Seeking Behavior in Rats

Burmeister

Lungren

Kirschner

et al. 2003

Neuropsychopharmacol

101

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The 5-HT indirect agonist, d-fenfluramine, attenuates cue reinstatement of extinguished cocaine-seeking behavior. To investigate the role of 5-HT receptor subtypes in this effect, we examined whether the attenuation is reversed by either a 5-HT 1A , 5-HT 2A/C , or 5-HT 2C receptor antagonist. We also examined the effects of the antagonists alone on both cue and cocaine-primed reinstatement. Rats that had been trained to press a lever for cocaine (0.75 mg/kg/0.1 ml, i.v.) paired with light and tone cues underwent daily extinction sessions during which responding had no consequences. We then examined the effects of WAY 100635 (0-1.0 mg/kg, s.c.), ketanserin (0-10.0 mg/kg, i.p.), or SB 242,084 (0-1.0 mg/kg, i.p.) with and without d-fenfluramine (1.0 mg/kg, i.p.) pretreatment on cue reinstatement. Subsequently, we examined the effects of the antagonists on cocaine-primed (7.5 or 15.0 mg/kg, i.p.) reinstatement. The 5-HT 1A antagonist, WAY 100635, failed to alter cue reinstatement, but attenuated cocaine reinstatement. Conversely, the 5-HT 2A/C antagonist, ketanserin, attenuated cue reinstatement, but failed to alter cocaine reinstatement. The 5-HT 2C -selective antagonist, SB 242,084, did not alter cue or cocaine reinstatement, but was the only drug that reversed the d-fenfluramine-induced attenuation of cue reinstatement. The findings suggest that stimulation of 5-HT 1A receptors plays a critical role in cocaine-primed, but not cue, reinstatement. Furthermore, 5-HT 2A and 5-HT 2C receptors may play oppositional roles in cue reinstatement. The SB 242,084 reversal of the d-fenfluramine attenuation suggests that stimulation of 5-HT 2C receptors inhibits cue reinstatement, whereas the ketanserin-induced attenuation of cue reinstatement suggests that decreased stimulation of 5-HT 2A receptors inhibits this behavior.

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“…tricyclics (amitriptyline, imipramine), mianserin, nefazodone, opipramole, trazodone [67,152,153] and fluoxetine [148,154]. Based on those findings, Di Matteo and colleagues [155] have carried out experiments showing that acute administration of amitriptyline and mianserin enhances DA release in the rat nucleus accumbens by blocking 5-HT 2C receptor subtypes. However, these drugs have multiple receptor and transporter interactions and it is difficult to asses what the real contribution of the 5-HT 2C receptor blockade is to the total clinical activity of the drugs.…”

Section: -Ht 2c Recptors and Depressionmentioning

confidence: 99%

Central Serotonin2C Receptor: From Physiology to Pathology

Giovanni¹,

Matteo²,

Pierucci³

et al. 2006

CTMC

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Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has explored the pathophysiological role of one of these receptors, the 5-HT 2C receptor, that has been emerged as a prominent central serotonin receptor subtype. The physiology, pharmacology and anatomical distribution of the 5-HT 2C receptors in the CNS will be firstly reviewed. Finally, their potential involvement in the pathophysiology of depression, schizophrenia, Parkinson's disease and drug abuse will be also discussed.Keywords: Serotonergic receptors, Depression, Schizophrenia, Drug of abuse, selective 5-HT 2C drugs. BASIC ANATOMY OF 5-HT SYSTEMMore than fifty years have passed since Twarog and Page [1] isolated an indole, identified as serotonin (5-HT), in the mammalian brain. Subsequently, Brodie and colleagues [2] suggested that 5-HT might serve as a neurotransmitter in the central nervous system (CNS). The result was one of the most important discoveries in science, giving birth to a new branch of neuroscience [3]. Serotonin is one of the oldest biologically active compound on earth, found in a variety of plants and animals. In vertebrates, the majority of the neurons containing 5-HT are grouped in 9 nuclei named B1 to B9, located in the medial part of the brainstem, generically called the raphe nuclei [4] (Fig. 1). These midline clusters can be divided into two major groups. The caudal or inferior group, localized in the medulla, contains the three nuclei projecting essentially to the grey matter of the spinal cord: the nucleus raphe magnus (NRM, cell group B5), nucleus raphe obscurus (NRO, cell groups B1-B2-B3), and nucleus raphe pallidus (NRP, cell group B4). The rostral or superior group, situated in the pons/mesenchephalon, contains the dorsal raphe nucleus (DRN, cell groups B6 and B7) and the median raphe nucleus (MRN, cell group B8). These nuclei supply about 80% of the serotonergic innervation of the forebrain. Even if in many brain areas, the innervation coming from the two nuclei overlaps, in certain regions the innervation comes exclusively or prevalently from one nucleus only. For example, the dorsal hippocampus receives a serotonergic innervation only from MRN, other areas innervated preferentially from this nucleus are: the medial preoptic area, the suprachiasmatic nucleus, the olfactory bulb *Address correspondence to this author at the Istituto di Ricerche Farmacologiche "Mario Negri", Consor...

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Acute administration of amitriptyline and mianserin increases dopamine release in the rat nucleus accumbens: possible involvement of serotonin 2C receptors

Cited by 56 publications

References 41 publications

Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

Alterations in blood glucose levels under hyperinsulinemia affect accumbens dopamine

Differential Roles of 5-HT Receptor Subtypes in Cue and Cocaine Reinstatement of Cocaine-Seeking Behavior in Rats

Central Serotonin2C Receptor: From Physiology to Pathology

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