Activation of serotonin 5-HT2A receptors inhibits high compulsive drinking on schedule-induced polydipsia

Navarro, Silvia; Gutiérrez-Ferre, Valeria E.; Flores, Pilar; Moreno, Margarita

doi:10.1007/s00213-014-3699-7

Cited by 26 publications

(23 citation statements)

References 68 publications

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“…After 20 daily sessions of SIP, the animals were separated into 2 specific populations, HD and LD, according to whether their rates of drinking were above or below the group median, respectively. 20,40 The following measures were recorded for each rat: (a) total amount of water (milliliters) removed from the bottle, (b) total licks to the bottle and (c) total entries into the food magazine (supplementary methods).…”

Section: Methodsmentioning

confidence: 99%

“…For example, the behavioral response to a challenge with dopaminergic drugs, such as D-amphetamine and cocaine, 37 diverges in the availability of dopamine D 1 and D 2 receptors in mesolimbic brain areas 38 ; lack of inhibitory control in the 5-choice serial reaction time task (5-CSRTT); increased serotonin and noradrenalin activity in the amygdala in post-mortem brain analyses 39 ; and a reduction of compulsive drinking by the 5-HT 2A/C serotonin agonist DOI in HD rats. 40 HD rats selected by SIP have shown behavioral and neurochemical alterations that are characteristic of inhibitory control deficits; however, the knowledge of the possible co-occurrence with other behavioral biomarkers of schizophrenia remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Navarro

Álvarez

Colomina

et al. 2016

Schizophrenia Bulletin

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Psychogenic polydipsia, which is compulsive, non-regulatory fluid consumption, is present in 6%–20% of chronic psychiatric patients and frequently associated with the schizophrenia diagnosis. In the present study, we investigated the relation between schizophrenia-like symptoms and biomarkers with a compulsive drinking behavior phenotype in rats. Rats that were selected for low drinking vs high drinking behavior following schedule-induced polydipsia (SIP) were assessed in a latent inhibition (LI) paradigm using tone and electrical foot shock and in a spatial reversal learning task to evaluate behavioral inflexibility. We also analyzed the myelin basic protein in different brain areas of high drinker (HD) and low drinker (LD) rats. The HD rats, which were characterized by a compulsive drinking behavior on SIP, had a reduced level of LI effect and increased behavioral inflexibility in the spatial reversal learning task in comparison to the LD group. Moreover, HD rats showed less myelination in the center of the corpus callosum, striatum, and amygdala in comparison to LD rats. These findings strengthen the validity of HD rats that were selected by SIP as a possible phenotype of compulsive neuropsychiatric disorders, as evidenced by the existence of behaviors and biological markers that are related to schizophrenia and obsessive-compulsive disorder, including a reduced LI effect, behavioral inflexibility and reduced brain myelination. Future studies could contribute to the elucidation of the mechanisms underlying the compulsive phenotype of HD rats and its relation to vulnerability to schizophrenia.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Navarro

Álvarez

Colomina

et al. 2016

Schizophrenia Bulletin

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“…This suggests that the responses to previously rewarded stimuli that are no longer reinforced are difficult to stop in animals with low levels of 5-HT. The influence of 5-HT on impulsive/compulsive actions involves several 5-HTRs including 5-HT 2A R and 5-HT 2C R [129,132,[206][207][208][209][210].…”

Section: Impulsive/compulsive Dimension and Behavioral Flexibilitymentioning

confidence: 99%

Serotonin in Animal Cognition and Behavior

Bacqué-Cazenave

Bharatiya

Barrière

et al. 2020

IJMS

218

111

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Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator of nervous systems in both invertebrates and vertebrates. It has been proposed for several decades that it impacts animal cognition and behavior. In spite of a completely distinct organization of the 5-HT systems across the animal kingdom, several lines of evidence suggest that the influences of 5-HT on behavior and cognition are evolutionary conserved. In this review, we have selected some behaviors classically evoked when addressing the roles of 5-HT on nervous system functions.In particular, we focus on the motor activity, arousal, sleep and circadian rhythm, feeding, social interactions and aggressiveness, anxiety, mood, learning and memory, or impulsive/compulsive dimension and behavioral flexibility. The roles of 5-HT, illustrated in both invertebrates and vertebrates, show that it is more able to potentiate or mitigate the neuronal responses necessary for the fine-tuning of most behaviors, rather than to trigger or halt a specific behavior. 5-HT is, therefore, the prototypical neuromodulator fundamentally involved in the adaptation of all organisms across the animal kingdom.The organization of the 5-HT systems is completely different between species ranging from a limited number of cells in Aplysia or Drosophila (100 5-HT immunoreactive cells) to several thousand neurons in vertebrates. The variety and the heterogeneity of 5-HT neurons have been highlighted in vertebrates [7] as well as in invertebrates [8]. In general, the 5-HT systems in animals comprise 5-HT neurons, which share a particular shape made of thousands of varicosities, leading to the concept of volume transmission [9], and several 5-HT receptors (5-HTRs). In vertebrates, 5-HT neurons are localized in the midbrain raphe nuclei described as the B1-B9 cell groups [1,10]. The raphe pallidus, obscurus, and pontis form a caudal cluster (B1-B5), whereas the dorsal raphe and median raphe form a rostral cluster in the pons (B6-B9) [11]. The caudal raphe group projects to the spinal cord and the rostral group to the forebrain via an extensive and diffuse innervation. The dorsal raphe nucleus contains the highest number of 5-HT neurons and its anatomical sub-regions display some degrees of specific innervation of the forebrain [12][13][14]. The median and dorsal raphe nuclei receive excitatory and inhibitory inputs from most brain areas [15]. In crustaceans or insects, 5-HT neurons are widely present in each of the ventral cord ganglia, display large local ramifications that act in multiple neuropil areas, and some axonal branches form three pairs of rostrocaudal fibers [16][17][18][19]. Presumably, two of those fibers would project anteriorly and one posteriorly to the entire nervous system [20]. 5-HT neurons are often localized close to sensory integration input area in the brain of arthropods and some 5-HT cells in the abdominal ganglia of crayfish nerve cord are sensitive to the mechanical stimulation of abdominal segmental fringe hairs [21]. In cnidarians, 5-HT cells ...

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“…These findings suggest that tandospirone reduces 5-HT neurotransmissions within the first week, probably via its agonistic activity toward serotonin autoreceptors, which may exacerbate compulsive drinking behavior in potentially or mildly polydipsic patients. Moreover, the reduction in water intake produced by 5-HT agonists was blocked by 5-HT 2A receptor antagonists, but not by 5-HT 2C receptor antagonists, in rats with highly compulsive drinking behavior [2].…”

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confidence: 84%

“…One possibility is that tandospirone may have altered serotonin (5-hydroxytryptamine: 5-HT) transmission in the brain, which may be linked to compulsive behavior. A more likely possibility is that 5-HT stimulants effectively reduce compulsive drinking in schedule-induced polydipsia, which is an established model for studies on compulsive behavior in rats [2]. Tandospirone acts as a potent and selective 5-HT 1A receptor partial agonist with approximately 55-85% intrinsic activity [3].…”

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confidence: 99%

Cerebral edema secondary to psychogenic polydipsia induced by tandospirone as add-on to olanzapine therapy

Nagamine¹

2014

CNPT

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Psychogenic polydipsia is not a rare complication in patients with schizophrenia, and has been recognized as a dangerous and potentially life-threatening disorder. Although multiple factors have been implicated, possibly including hypothalamic dysfunction, syndrome of inappropriate secretion of ADH (SIADH), and adverse medication effects, the underlying pathophysiology of psychogenic polydipsia is still unclear [1]. The author encountered a case of cerebral edema secondary to psychogenic polydipsia possibly related to the coadministration of tandospirone with olanzapine, which seems to reduce serotonergic activity, probably via its agonistic activity toward serotonin autoreceptors. A 69-year-old female inpatient with schizophrenia was found with unconsciousness and generalized tonic clonic seizures 3 days after the initiation of tandospirone as add-on to olanzapine therapy. She had been diagnosed as schizophrenic since she was in her twenties, after her first psychotic break, and had been treated with several medications with varying degrees of success. Recently, her delusions had been well controlled by olanzapine 20 mg/day. Although she had been mildly but chronically polydipsic for many years, severe hyponatremia and convulsions had not been observed. Tandospirone 20 mg/day was added to olanzapine for the treatment of psychotic depression. However, she experienced convulsions 3 days after the initiation of tandospirone. A nasogastric tube was inserted, and a large amount of clear liquid was removed from her stomach. The patient's initial serum sodium level was 112 mmol/L, representing a marked decrease from the level of 142 mmol/L 20 days earlier ( Fig.1) A non-contrast computed tomographic scan of the patient's brain revealed a loss of gray-white differentiation and sulcal effacement, consistent with cerebral edema. She was diagnosed as having acute hyponatremia, presumably secondary to psychogenic polydipsia. Based on the clinical severity of the cerebral edema, she was treated with the rapid infusion of normal saline and a loop diuretic at the rate required for sodium correction of 1.0 mmol/L/hr while her serum sodium level was closely monitored. The patient's serum sodium level rapidly increased from 112 mmol/L to 131 mmol/L in 24 hours, and she excreted 7.2 liters of urine in 24 hours. On day 3, the patient was awake and alert, and recovered her orientation to person, place and time, as her sodium level recovered to 137 mmol/L. However, after the patient's hyponatremia was corrected, she developed a substantial elevation in her creatine kinase (CK) level, indicating rhabdomyolysis, possibly due to the calcium-sodium exchange mechanism across the skeletal myocyte or the failure of cell volume regulation secondary to extracellular hypo-osmolality. Fortunately, the asymptomatic rhabdomyolysis resolved without treatment on day 9, and the patient's overall condition was good, and she did not experience any additional seizures (Fig. 1). .

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Activation of serotonin 5-HT2A receptors inhibits high compulsive drinking on schedule-induced polydipsia

Cited by 26 publications

References 68 publications

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Serotonin in Animal Cognition and Behavior

Cerebral edema secondary to psychogenic polydipsia induced by tandospirone as add-on to olanzapine therapy

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