5-HT 3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not methylphenidate-induced neurochemical and behavioral effects in the rat

Kankaanpää, Aino; Meririnne, Esa; Seppαlä, Timo

doi:10.1007/s00213-001-0939-4

Cited by 61 publications

(49 citation statements)

References 54 publications

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“…Furthermore, mice that overexpress the 5-HT 3 receptor are more sensitive to the locomotor activating effect of cocaine but less sensitive to the reinforcing effects of cocaine in conditioned place preference (Allan et al, 2001). Systemically administered 5-HT 3 antagonists reduce cocaine-induced DA release in the Acb and decrease cocaine-induced condition place preference and locomotor activity (Kankaanpaa et al, 2002). Therefore, the current findings extend previous research indicating the ability of the 5-HT 3 receptor to modulate the effects of cocaine.…”

Section: Discussionsupporting

confidence: 86%

Intracranial Self-Administration of Cocaine within the Posterior Ventral Tegmental Area of Wistar Rats: Evidence for Involvement of Serotonin-3 Receptors and Dopamine Neurons

Rodd

Bell²,

Kuc

et al. 2005

J Pharmacol Exp Ther

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The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine (DA) system. The present study assessed whether adult female Wistar rats would self-administer cocaine directly into the ventral tegmental area (VTA). Following guide cannulae surgery aimed at either the posterior or anterior VTA, subjects were placed in an operant box equipped with an active lever that caused the delivery of the infusate and an inactive lever that did not. Posterior and anterior VTA subjects were randomly assigned to one of six groups that self-administered either artificial cerebrospinal fluid (aCSF) or 25 to 400 pmol cocaine/100 nl in aCSF for the first four sessions, aCSF in sessions 5 and 6, and the acquisition dose of infusate during session 7. Additionally, the effects of increasing the time-out period, higher concentrations of cocaine, coadministration of a 5HT 3 antagonist, and coadministration of a D 2/3 agonist on self-infusion of cocaine were determined. Self-infusions were maintained when the time-out period was extended from 5 to 25 s. Coinfusion of a 5HT 3 antagonist or D 2/3 agonist blocked the self-infusion of cocaine. In contrast, rats did not self-administer 25 to 400 pmol/100 nl cocaine into the anterior VTA. Additionally, rats did not selfadminister either 800 or 1600 pmol/100 nl cocaine into the posterior or anterior VTA. Overall, the data indicate that the VTA is functionally heterogeneous with regard to the rewarding actions of cocaine and that the reinforcing effects of cocaine within the posterior VTA are mediated by activation 5-HT 3 receptors and DA neurons.

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Section: Discussionsupporting

confidence: 86%

Intracranial Self-Administration of Cocaine within the Posterior Ventral Tegmental Area of Wistar Rats: Evidence for Involvement of Serotonin-3 Receptors and Dopamine Neurons

Rodd

Bell²,

Kuc

et al. 2005

J Pharmacol Exp Ther

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“…5-HT 2C receptors and DA outflow S Navailles et al 5-HT 2C receptors may unmask excitatory and phasic influences on DA outflow exerted by endogenous 5-HT via other 5-HT receptors, as already shown in case of concomitant increase in DA and 5-HT transmission (Kankaanpää et al, 2002;Bubar et al, 2003;Porras et al, 2003). Additional experiments are warranted to evaluate this possibility.…”

Section: Discussionmentioning

confidence: 92%

In Vivo Evidence that 5-HT2C Receptor Antagonist but not Agonist Modulates Cocaine-Induced Dopamine Outflow in the Rat Nucleus Accumbens and Striatum

Navailles

Deurwaerdère

Porras

et al. 2003

Neuropsychopharmacol

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During recent years, much attention has been devoted at investigating the modulatory role of central 5-HT 2C receptors on dopamine (DA) neuron activity, and it has been proposed that these receptors modulate selectively DA exocytosis associated with increased firing of DA neurons. In the present study, using in vivo microdialysis in the nucleus accumbens (NAc) and the striatum of halothaneanesthetized rats, we addressed this hypothesis by assessing the ability of 5-HT 2C agents to modulate the increase in DA outflow induced by haloperidol and cocaine, of which the effects on DA outflow are associated or not with an increase in DA neuron firing, respectively. The intraperitoneal administration of cocaine (10-30 mg/kg) induced a dose-dependent increase in DA extracellular levels in the NAc and the striatum. The effect of 15 mg/kg cocaine was potentiated by the mixed 5-HT 2C/2B antagonist SB 206553 (5 mg/kg i.p.) and the selective 5-HT 2C antagonist SB 242084 (1 mg/kg i.p.) in both brain regions. The mixed 5-HT 2C/2B agonist, Ro 60-0175 (1 mg/kg i.p.), failed to affect cocaine-induced DA outflow, but reduced significantly the increase in DA outflow induced by the subcutaneous administration of 0.1 mg/kg haloperidol. The obtained results provide evidence that 5-HT 2C receptors exert similar effects in both the NAc and the striatum, and they modulate DA exocytosis also when its increase occurs independently from an increase in DA neuron impulse activity. Furthermore, they show that 5-HT 2C agonists, at variance with 5-HT 2C antagonists, exert a preferential control on the impulse-stimulated release of DA.

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“…While it is clear that 5-HT3 receptors modulate phasic DA release in the NA, some conflicting results exist for acute treatments of particular drugs. For example, systemic administration of the 5-HT3 antagonists MDL 72222, ondansetron and zacopride has been shown to attenuate the increases in NA DA induced by cocaine (McNeish et al, 1993;Kankaanpaa et al, 2002), and haloperidol (De Deurwaerdere et al, 2005). However, other studies have shown that systemic administration of the 5-HT3 antagonists MDL 72222 and ondansetron had no effect on the increase in NA DA induced by cocaine (De Deurwaerdere et al, 2005), haloperidol (Koulu et al, 1989) or amphetamine (De Deurwaerdere et al, 2005).…”

Section: Mesolimbic Pathwaymentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

526

317

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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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5-HT 3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not methylphenidate-induced neurochemical and behavioral effects in the rat

Cited by 61 publications

References 54 publications

Intracranial Self-Administration of Cocaine within the Posterior Ventral Tegmental Area of Wistar Rats: Evidence for Involvement of Serotonin-3 Receptors and Dopamine Neurons

Intracranial Self-Administration of Cocaine within the Posterior Ventral Tegmental Area of Wistar Rats: Evidence for Involvement of Serotonin-3 Receptors and Dopamine Neurons

In Vivo Evidence that 5-HT2C Receptor Antagonist but not Agonist Modulates Cocaine-Induced Dopamine Outflow in the Rat Nucleus Accumbens and Striatum

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

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