Different regulation of rat 5-HT2A and rat 5-HT2C receptors in NIH 3T3 cells upon exposure to 5-HT and pipamperone

Oekelen, Dirk Van; Jurzak, Mirek; Wiel, D Van de; Hecke, Geert Van; Luyten, Walter; Leysen, Josée E.

doi:10.1016/s0014-2999(01)01170-0

Cited by 11 publications

(6 citation statements)

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“…As a reduction in 5-HT 2A receptor-mediated responses can be associated with down-regulation of the receptors (e.g., Leysen et al, 1989;Grotewiel and Sanders-Bush, 1994;Van Oekelen et al, 2001), the premise of the present study was that brain regions containing altered expression of 5-HT 2A receptors in the context of a similar alteration in DOM-induced stimulus control might be important in mediating the discriminative stimulus effects of phenethylamine hallucinogens. Further, the use of two dissimilar compounds to alter the behavior response should lessen the chance of spurious correlations.…”

Section: Discussionmentioning

confidence: 91%

“…Because chronic exposure to agonists was reported to decrease 5-HT 2A receptor-mediated phosphoinositide hydrolysis with no change (Roth et al, 1995) or an increase in 5-HT 2A receptor levels (Akiyoshi et al, 1993;Van Oekelen et al, 2001), the observed behavioral tolerance could involve an impairment in the signaling machinery rather than down-regulation of the receptor. Furthermore, chronic treatment with DOM and clozapine might be acting through entirely different mechanisms to reduce the stimulus effects of DOM.…”

Section: Discussionmentioning

confidence: 99%

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Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Doat-Meyerhoefer

Hard

Winter

et al. 2005

Pharmacology Biochemistry and Behavior

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Activation of 5-HT 2A receptors has been shown to be an essential component of the discriminative stimulus effects of indoleamine and phenethylamine hallucinogens. The objective of the present study was to determine the neuroanatomical location of the 5HT 2A receptors which may be responsible for the stimulus effects of the phenethylamine hallucinogen [−]2,5-dimethoxy-4-methylamphetamine (DOM). It was hypothesized that brain areas containing altered 5-HT 2A receptor expression in the context of a similar alteration in DOM-induced stimulus control might be important in mediating the stimulus effects of DOM. Fisher 344 rats were treated with either clozapine (25 mg/kg/day) or DOM (2 mg/kg/day) for 7 days, and the consequences of these drug treatment regimens on DOM-induced stimulus control and on 5-HT 2A receptor expression in several brain areas were determined. Chronic administration of clozapine was associated with a wide-spread decrease in levels of 5-HT 2A/2C receptors. Conversely, treatment with DOM had varied effects including a neuroanatomically selective decrease in 5-HT 2A/2C receptors levels that was restricted to the olfactory nucleus. Both chronic treatment with DOM and clozapine decreased the stimulus effects of DOM. The present findings suggest a role for the olfactory nucleus in producing the stimulus effects of DOM.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Doat-Meyerhoefer

Hard

Winter

et al. 2005

Pharmacology Biochemistry and Behavior

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“…In vitro studies have shown that 5-HT 2A receptors are acutely desensitized, as measured by PI turnover, after as little as 15 min exposure to 5-HT (Kagaya et al, 1990;Van Oekelen et al, 2001). …”

Section: Behavioral Assessments Of 5ht 2a/c Receptorsmentioning

confidence: 99%

Regulation of 5-HT2A/C receptors and DOI-induced behaviors by protein kinase Cγ

Bowers

Miyamoto‐Ditmon

Wehner

2006

Pharmacology Biochemistry and Behavior

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Protein kinase C γ (PKCγ) null mutant mice demonstrate increased behavioral impulsivity and ethanol consumption. Pharmacological studies have shown that 5-HT 2A/C receptors modulate impulsivity and ethanol consumption in rodents and that PKC can regulate 5-HT 2A/C receptors. To determine whether PKCγ plays a selective role in 5-HT 2A/C receptor regulation, biochemical and behavioral experiments were performed in PKCγ mutant and wild-type mice. DOI-stimulated phosphoinositol hydrolysis and [ 125 I]-DOI saturation binding in the PFC, and quantitative autoradiography of [ 125 I]-DOI binding sites in 15 brain regions were analyzed. DOI-induced head twitch responses (HTR) were measured in naïve mice after an acute 2.5 mg/kg injection of DOI. Results indicated that DOI-induced HTR was significantly greater in mutant mice compared to wildtype mice. Results of the phosphoinositol hydrolysis, membrane binding, and autoradiography experiments indicated that in mutant mice, increased HTR was associated with increased 5-HT 2A/C receptor function in the PFC, but not increased receptor number or affinity suggesting that PKCγ regulates receptor function but not receptor number. These data support a role for 5-HT 2A/C receptors in the PFC in mediating some of the behavioral differences observed between PKCγ mutant and wild-type mice.

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“…Another sequel of the increased synaptic 5-HT release could be downregulation or internalization of 5-HT 2A . However, the in vitro study from Van Oekelen et al demonstrated that cell pretreatment with 5-HT for 15 min and 48 h did not provoke reduced 5-HT 2A numbers (33). This finding pleads against downregulation or internalization of 5-HT 2A by morphine-invoked release of 5-HT.…”

Section: Discussionmentioning

confidence: 96%

The Influence of Morphine on Cerebral 5-HT_2A Availability in Dogs: a SPECT Study

et al. 2012

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The opioid and serotonergic systems are closely involved in pain processing and mood disorders. The aim of this study was to assess the influence of systemic morphine on cerebral serotonin 2A receptor (5-HT 2A ) binding in dogs using SPECT with the 5-HT 2A radioligand 123 I-5I-R91150. Methods: 5-HT 2A binding was estimated with and without morphine pretreatment in 8 dogs. The 5-HT 2A binding indices in the frontal, parietal, temporal, and occipital cortex and in the subcortical region were obtained by semiquantification. Results: A significantly decreased 5-HT 2A binding index was found in the morphine group for the right (morphine, 1.41 6 0.06; control, 1.52 6 0.10) and left (morphine, 1.44 6 0.08; control, 1.55 6 0.11) frontal cortices, with P 5 0.012 and P 5 0.040, respectively. No significant differences were noted for the other regions. Conclusion: Morphine decreased the frontocortical 5-HT 2A availability, confirming an interaction between the 5-HTergic and the opioid systems. Whether this interaction is caused by decreased receptor density due to direct internalization or is the result of indirect actions, such as increased endogenous serotonin release, remains to be elucidated.Key Words: serotonin (5-HT); 5-HT 2A ; morphine; SPECT; frontal cortex Nucl Med 2012; 53:1969 53: -1973 53: DOI: 10.2967 It is well documented that there is a close interaction between the brain opioid and serotonin (5-hydroxytryptamine [5-HT]) neurotransmitter systems (1-3). Activation of the m-opioid receptor system leads to 5-HTergic changes, including increased release of synaptic 5-HT, as was shown in several brain regions and in the spinal cord in various in vivo microdialysis studies (1,2). Furthermore, pharmacologic and behavioral studies pointed out that the 5-HTergic system is implicated in spinal pain transmission, modulation, and control and particularly in the mediation of opioid analgesia (3,4). Morphine-induced analgesia is thought to rely in part on the indirect activation of descending inhibitory 5-HTergic pathways (3). Consequently, antidepressants that inhibit 5-HT reuptake, such as fluvoxamine and fluoxetine, are also known to have analgesic properties, especially in chronic pain states (5,6). JBeside its role in pain modulation (7-9), 5-HT 2A receptor (5-HT 2A ) gained interest over the last few decades due to its involvement in several neurologic disorders in humans, including anxiety (10), depression (11), schizophrenia (12), and obsessive-compulsive disorder (13). More specifically, atypical antipsychotic drugs acting as 5-HT 2A antagonists and inverse agonists were seen to be effective in reducing the symptoms of these diseases (10,14). Because the opioid system has been shown to be involved in several of these mood disorders as well (15), the interaction between m-opioid receptors and 5-HT 2A at an emotional or cognitive level gained interest, partly with regard to common opioid side effects such as tolerance and addiction that are thought to have a 5-HTergic component as well. Consequently, several in v...

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Different regulation of rat 5-HT2A and rat 5-HT2C receptors in NIH 3T3 cells upon exposure to 5-HT and pipamperone

Cited by 11 publications

References 25 publications

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Regulation of 5-HT2A/C receptors and DOI-induced behaviors by protein kinase Cγ

The Influence of Morphine on Cerebral 5-HT_2A Availability in Dogs: a SPECT Study

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Different regulation of rat 5-HT2A and rat 5-HT2C receptors in NIH 3T3 cells upon exposure to 5-HT and pipamperone

Cited by 11 publications

References 25 publications

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas

Regulation of 5-HT2A/C receptors and DOI-induced behaviors by protein kinase Cγ

The Influence of Morphine on Cerebral 5-HT2A Availability in Dogs: a SPECT Study

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Product

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The Influence of Morphine on Cerebral 5-HT_2A Availability in Dogs: a SPECT Study