5-HT2 receptors differentially modulate dopamine-mediated auto-inhibition in A9 and A10 midbrain areas of the rat

Olijslagers, J.E.; Werkman, T.R.; McCreary, Andrew C.; Siarey, Richard J.; Kruse, CG; Wadman, Wytse J.

doi:10.1016/j.neuropharm.2003.10.003

Cited by 33 publications

(16 citation statements)

References 31 publications

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“…As 5-HT 1B receptors depress presynaptic 5-HT release, lithium's elevation of k* for AA in auditory and visual areas may result from derepressed 5-HT release, elevated 5-HT in the cleft, or an increased 5-HT 2A/2C -mediated activation of PLA 2 (Januel et al, 2002;Redrobe and Bourin, 1999). A similar effect can occur in the substantia nigra and locus coeruleus, where 5-HT 2A and 5-HT 1B receptors are found (Aghajanian and Marek, 1999;Olijslagers et al, 2004;Sijbesma et al, 1991). On the other hand, lithium is reported not to change whole brain 5-HT turnover (Karoum et al, 1997), 5-HT release (Mork, 1998;Sharp et al, 1991), DOIinduced adrenocorticotropic hormone (ACTH) release (Gartside et al, 1992), or DOI-evoked wet-dog shakes in ACTH-treated rats (Kitamura et al, 2002).…”

Section: Discussionmentioning

confidence: 97%

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Basselin

Chang

Seemann

et al. 2004

Neuropsychopharmacol

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The effects of chronic lithium administration on regional brain incorporation coefficients k* of arachidonic acid (AA), a marker of phospholipase A 2 (PLA 2 ) activation, were determined in unanesthetized rats administered i.p. saline or 1 mg/kg i.p. (7)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a 5-HT 2A/2C receptor agonist. After injecting [1-14 C]AA intravenously, k* (brain radioactivity/integrated plasma radioactivity) was measured in each of 94 brain regions by quantitative autoradiography. Studies were performed in rats fed a LiCl or a control diet for 6 weeks. In the control diet rats, DOI significantly increased k* in widespread brain areas containing 5-HT 2A/2C receptors. In the LiCl-fed rats, the significant positive k* response to DOI did not differ from that in control diet rats in most brain regions, except in auditory and visual areas, where the response was absent. LiCl did not change the head turning response to DOI seen in control rats. In summary, LiCl feeding blocked PLA 2 -mediated signal involving AA in response to DOI in visual and auditory regions, but not generally elsewhere. These selective effects may be related to lithium's therapeutic efficacy in patients with bipolar disorder, particularly its ability to ameliorate hallucinations in that disease.

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Section: Discussionmentioning

confidence: 97%

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Basselin

Chang

Seemann

et al. 2004

Neuropsychopharmacol

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“…Electrophysiological studies, for instance, have shown that M100907, a selective 5-HT2a antagonist, attenuates amphetamine and quinpirole-induced inhibition of ventral midbrain DA cell firing. It also produces a strong potentiation of the reversal effect of the selective D2 antagonist, sulpiride, on quinpirole-induced inhibition (Olijslagers et al, 2004(Olijslagers et al, , 2005. Activation of 5-HT2a receptors potentiates amphetamine-induced ventral striatal and medial prefrontal cortex (PFC) DA release, an effect prevented by M100907 (Kuroki et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Blockade of 5-HT2a Receptors Reduces Haloperidol-Induced Attenuation of Reward

Benaliouad

Kapur

Rompré

2006

Neuropsychopharmacol

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Previous studies have shown that effective antipsychotic medications attenuate reward, an effect that is generally attributed to their effectiveness at blocking the dopamine D2-like receptors. As blockade of the serotonin type 2a (5-HT2a) receptors is a common property of the newer antipsychotics, the present study compared the effect of haloperidol, clozapine, and M100907 (a selective 5-HT2a antagonist) and the combined effect of haloperidol and M100907 treatment on brain stimulation reward (BSR). Experiments were performed on male Sprague-Dawley rats trained to produce an operant response to obtain electrical stimulation in the lateral hypothalamus. Measures of reward threshold were determined in different groups of rats using the curve-shift method using fixed current intensity and variable frequency before and at different times after injection of haloperidol (0.01, 0.05, 0.1, and 0.25 mg/kg), clozapine (1, 7.5, 15, and 30 mg/kg), M100907 (0.033, 0.1, and 0.3 mg/kg), or their vehicle. The effect of M100907 (0.3 mg/kg) on the attenuation of BSR by a sub-and suprathreshold dose of haloperidol was studied in another group of rats. Clozapine produced a dose-orderly increase in reward threshold with a mean maximal increase of 50%; at high doses, clozapine induced cessation of responding in several animals at different time periods. Haloperidol induced a dose-dependent increase in reward threshold, with the mean maximal increase (75%) being observed at the highest dose; it also produced a dose-dependent reduction of maximum rates of responding. M100907 failed to alter reward at any of the doses tested and had no effect on the subthreshold dose (0.01 mg/kg) of haloperidol. But when combined with a suprathreshold dose of haloperidol, M100907 reduced the reward-attenuating effect of haloperidol. These results show that 5-HT2a receptors are unlikely to constitute a component of the reward-relevant pathway activated by lateral hypothalamic stimulation. However, blockade of 5-HT2a receptors may account for the relatively lower level of reward attenuation produced by clozapine, and predict that antipsychotic medications that have a high affinity for the 5-HT2a receptor may be less likely to induce dysphoria.

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“…DA D 2 receptor-mediated auto-inhibition can be enhanced by 5-HT 2 receptors in the VTA, but in the SN probably another 5-HT receptor type is involved [116] (Fig. (2)).…”

Section: Functional Mechanism Of 5-ht Modulation and Implications Formentioning

confidence: 99%

“…Furthermore, differential roles appear to exist for some 5-HT receptor types, such as the 5-HT 2 receptors, i.e. 5-HT 2C receptors change DA neuronal firing activity and bursting in VTA, but not in SN DA neurons [35,39,116], while 5-HT 4 receptors play a more pronounced role in SN DA neurons [90].…”

Section: -Ht and Sn And Vta Da Neuron Activitymentioning

confidence: 99%

“…Extracellular recordings of SN and VTA DA neurons in vitro have shown that concentrations of 5-HT that do not change the firing rate when applied alone enhanced DA D 2 receptor-mediated auto-inhibition [16,116]. It was demonstrated that this enhancement of auto-inhibition was mediated via different 5-HT receptors in the SN and VTA, with 5-HT 2 receptors being critically involved in the VTA, in line with in vivo findings that 5-HT 2 receptors differentially affect DA neuronal activity in SN and VTA [35,39].…”

Section: -Ht Modulation Of Da D 2 Receptor-mediated Inhibitionmentioning

confidence: 99%

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Modulation of Midbrain Dopamine Neurotransmission by Serotonin, a Versatile Interaction Between Neurotransmitters and Significance for Antipsychotic Drug Action

Olijslagers

Werkman²,

Mccreary³

et al. 2006

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Schizophrenia has been associated with a dysfunction of brain dopamine (DA). This, so called, DA hypothesis has been refined as new insights into the pathophysiology of schizophrenia have emerged. Currently, dysfunction of prefrontocortical glutamatergic and GABAergic projections and dysfunction of serotonin (5-HT) systems are also thought to play a role in the pathophysiology of schizophrenia. Refinements of the DA hypothesis have lead to the emergence of new pharmacological targets for antipsychotic drug development. It was shown that effective antipsychotic drugs with a low liability for inducing extra-pyramidal side-effects have affinities for a range of neurotransmitter receptors in addition to DA receptors, suggesting that a combination of neurotransmitter receptor affinities may be favorable for treatment outcome.This review focuses on the interaction between DA and 5-HT, as most antipsychotics display affinity for 5-HT receptors. We will discuss DA/5-HT interactions at the level of receptors and G protein-coupled potassium channels and consequences for induction of depolarization blockade with specific attention to DA neurons in the ventral tegmental area (VTA) and the substantia nigra zona compacta (SN), neurons implicated in treatment efficacy and the side-effects of schizophrenia, respectively. Moreover, it has been reported that electrophysiological interactions between DA and 5-HT show subtle, but important, differences between the SN and the VTA which could explain (in part) the effectiveness and lower propensity to induce side-effects of the newer atypical antipsychotic drugs. In that respect the functional implications of DA/5-HT interactions for schizophrenia will be discussed.Key Words: Schizophrenia, antipsychotic drug, substantia nigra, ventral tegmental area. DOPAMINE AND SCHIZOPHRENIAThe mesocortical pathway, the mesolimbic pathway, the nigrostriatal pathway and the tuberoinfundibular pathway have all been postulated to be involved in the pathophysiology of schizophrenia and the propensity of antipsychotic drugs to induce side-effects [144]. Hypofunction of the mesocortical pathway and hyperfunction of the mesolimbic pathway [44,55,144] are thought to be responsible for the symptoms that can be observed (see also Sesack and Carr, 2002 [138])) and points to one of the many difficulties for effective treatment: increasing dopamine (DA) activity in the mesocortical pathway, while concomitantly decreasing DA activity in the mesolimbic pathway. The nigrostriatal and tuberoinfundibular pathways are involved in side-effects of antipsychotic drug treatment, such as extra-pyramidal side effects and hyperprolactinemia, respectively [10, 30] which are related to changes in firing activity of neurons in these pathways, especially the DA neurons. What lies at the root of this mesocortical mesolimbic dysfunction is unclear but loss of cholinergic interneurons in the striatum, hypoglutamatergia or "miswiring" of glutamatergic and _-amino butyric acid (GABA)-ergic projections from the prefrontal...

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5-HT2 receptors differentially modulate dopamine-mediated auto-inhibition in A9 and A10 midbrain areas of the rat

Cited by 33 publications

References 31 publications

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Blockade of 5-HT2a Receptors Reduces Haloperidol-Induced Attenuation of Reward

Modulation of Midbrain Dopamine Neurotransmission by Serotonin, a Versatile Interaction Between Neurotransmitters and Significance for Antipsychotic Drug Action

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