Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder

Boshuisen, M.L.; Boer, Johan A. den

doi:10.1007/s002130000529

Cited by 20 publications

(9 citation statements)

References 22 publications

(34 reference statements)

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“…This is a potential confounder of the data in that the drug may itself produce changes in brain structure and function, albeit intermittent use with the use with migraine attacks. While the direct effects of triptans are still a matter of debate (Tfelt-Hansen 2010), and longitudinal studies will be needed to clarify their impact on the central nervous system central nervous system central nervous system, there are studies supporting direct effects of triptans on CNS (Boshuisen and den Boer 2000; Cupini and Calabresi 2005; Dodick and Martin 2004). …”

Section: Discussionmentioning

confidence: 99%

Common hippocampal structural and functional changes in migraine

et al. 2012

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The hippocampus is classically involved in memory consolidation, spatial navigation and is involved in the stress response. Migraine is an episodic disorder characterized by intermittent attacks with a number of physiological and emotional stressors associated with or provoking each attack. Given that migraine attacks can be viewed as repeated stressors, alterations in hippocampal function and structure may play an important role in migraine pathophysiology. Using high-resolution magnetic resonance imaging, hippocampal morphometric and functional differences (in response to noxious heat stimulation) were compared in age and gender-matched acute episodic migraineurs with high (HF) versus low (LF) frequency of migraine attacks. Morphometric results were compared with age and gender-matched healthy control (HC) cohort. Significant larger bilateral hippocampal volume was found in LF group relative to the HF and HC groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency. Functional correlates of greater deactivation (LF > HF) in the same hippocampal regions in response to noxious stimulation was also accompanied by overall reduction in functional connectivity of the hippocampus with other brain regions involved in pain processing in the HF group. The results implicate involvement of hippocampus in the pathophysiology of the migraine.

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Section: Discussionmentioning

confidence: 99%

Common hippocampal structural and functional changes in migraine

et al. 2012

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“…Furthermore, CP94253 dose-dependently reduces the expression of conditioned freezing (McDevitt et al, 2011), suggesting that 5-HT 1B R agonists attenuate conditioned anxiety. Clinical research investigating the effects of the triptan class of 5-HT 1 R agonists on anxiety has yielded mixed result with some studies reporting no effects of acute administration of sumatriptan, a 5-HT 1A/1B/1D R agonist (Pian et al, 1998), or zolmitriptan, a 5-HT 1B/1D/1F R agonist (Boshuisen and den Boer, 2000) in patients with obsessive-compulsive disorder (OCD). However, others have reported symptom exacerbation in OCD patients using the same acute doses (Stern et al, 1998) and following chronic administration (Koran et al, 2001), suggesting that 5-HT 1B R agonists may be counter indicated for patients with OCD.…”

Section: Dysregulation Of 5-ht1brsmentioning

confidence: 99%

Dopamine D3 and 5-HT1B receptor dysregulation as a result of psychostimulant intake and forced abstinence: Implications for medications development

2014

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Addiction to psychostimulants, including cocaine and amphetamine, is associated with dysregulation of dopamine and serotonin (5-HT) neurotransmitter systems. Neuroadaptations in these systems vary depending on the stage of the drug taking-abstinence-relapse cycle. Consequently, the effects of potential treatments that target these systems may vary depending on whether they are given during abstinence or relapse. In this review, we discuss evidence that dopamine D3 receptors (D3Rs) and 5-HT1B receptors (5-HT1BRs) are dysregulated in response to both chronic psychostimulant use and subsequent abstinence. We then review findings from preclinical self-administration models which support targeting D3Rs and 5-HT1BRs as potential medications for psychostimulant dependence. Potential side effects of the treatments are discussed and attention is given to studies reporting positive treatment outcomes that depend on: 1) whether testing occurs during abstinence versus relapse, 2) whether escalation of drug self-administration has occurred, 3) whether the treatments are given repeatedly, and 4) whether social factors influence treatment outcomes. We conclude that D3/D2 agonists may decrease psychostimulant intake; however, side effects of D3/D2R full agonists may limit their therapeutic potential, whereas D3/D2R partial agonists likely have fewer undesirable side effects. D3-selective antagonists may not reduce psychostimulant intake during relapse, but nonetheless, may decrease motivation for seeking psychostimulants with relatively few side-effects. 5-HT1BR agonists provide a striking example of treatment outcomes that are dependent on the stage of the addiction cycle. Specifically, these agonists initially increase cocaine’s reinforcing effects during maintenance of self-administration, but after a period of abstinence they reduce psychostimulant seeking and the resumption of self-administration. In conclusion, we suggest that factors contributing to dysregulation of monoamine systems, including drug history, abstinence, and social context, should be considered when evaluating potential treatments to better model treatment effects in humans.

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“…Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and refers to the reduction in startle magnitude that occurs when an abrupt startling stimulus is preceded 30–500 msec by a barely detectable stimulus (8), and is reduced in OCD (6, 7). Second, pharmacological challenge with serotonin 1B receptor (5-HT 1B R) agonists exacerbates symptoms in OCD patients (9–11) (however, see (12)). Third, OCD patients exhibit overactivity of the orbitofrontal cortex (OFC) at rest (13–15) and following symptom provocation (16, 17) that is reversed by successful treatment (18–20).…”

Section: Introductionmentioning

confidence: 99%

Essential Role for Orbitofrontal Serotonin 1B Receptors in Obsessive-Compulsive Disorder-Like Behavior and Serotonin Reuptake Inhibitor Response in Mice

Shanahan

Velez

Masten

et al. 2011

Biological Psychiatry

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Background Perseveration and sensorimotor gating deficits are core features of obsessive-compulsive disorder (OCD). Serotonin 1B receptor (5-HT1BR) agonists exacerbate OCD symptoms in patients, and induce perseveration and sensorimotor gating deficits in mice. Serotonin reuptake inhibitors (SRIs), but not noradrenaline reuptake inhibitors (NRIs), reduce OCD symptoms following 4–8 weeks of treatment. Using mice, we compared the effects of chronic SRI versus NRI treatment on 5-HT1BR-induced OCD-like behavior, and 5-HT1BR sensitivity in orbitofrontal-subcortical “OCD circuits”. Furthermore, we localized the 5-HT1BR population that mediates OCD-like behavior. Methods Mice chronically received the SRI clomipramine or the NRI desipramine and were examined for 5-HT1BR-induced OCD-like behavior, or 5-HT1BR binding and G-protein-coupling in caudate-putamen, nucleus accumbens, and orbitofrontal cortex. Separate mice were tested for OCD- or depression-like behavior following 4, 14, 21, 28 or 56 days of SRI treatment. Finally, OCD-like behavior was assessed following intra-orbitofrontal 5-HT1BR agonist infusion, or intra-orbitofrontal 5-HT1BR antagonist infusion coupled with systemic 5-HT1BR agonist treatment. Results Effective, but not ineffective, OCD treatments reduced OCD-like behavior in mice with a time-course that parallels the delayed therapeutic onset in OCD patients, and downregulated 5-HT1BR expression in the orbitofrontal cortex. Intra-orbitofrontal 5-HT1BR agonist infusion induced OCD-like behavior, and intra-orbitofrontal 5-HT1BR antagonist infusion blocked OCD-like effects of systemic 5-HT1BR agonist treatment. Conclusions These results indicate that orbitofrontal 5-HT1BRs are necessary and sufficient to induce OCD-like behavior in mice, and that SRI pharmacotherapy reduces OCD-like behavior by desensitizing orbitofrontal 5-HT1BRs. Our findings suggest an essential role for orbitofrontal 5-HT1BRs in OCD pathophysiology and treatment.

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Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder

Cited by 20 publications

References 22 publications

Common hippocampal structural and functional changes in migraine

Common hippocampal structural and functional changes in migraine

Dopamine D3 and 5-HT1B receptor dysregulation as a result of psychostimulant intake and forced abstinence: Implications for medications development

Essential Role for Orbitofrontal Serotonin 1B Receptors in Obsessive-Compulsive Disorder-Like Behavior and Serotonin Reuptake Inhibitor Response in Mice

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