-
Journal of Family Medicine and Primary... Mar 2024This is a report of a series of three cases of trazodone-induced oral lingual dyskinesias. Each case demonstrated a distinct pattern of the development of this...
This is a report of a series of three cases of trazodone-induced oral lingual dyskinesias. Each case demonstrated a distinct pattern of the development of this dyskinesia after trazodone exposure for several months. All cases showed abrupt cessation of the movement disorder when the drug was discontinued. Two of the three cases had no prior exposure to any dopamine-blocking agents. One of the three had a distant exposure to a dopamine antagonist. Trazodone has a mechanism of action that can account for both the development and treatment of dyskinetic movements. This article will discuss proposed mechanisms for trazodone's action with an emphasis on case reports of dystonic movements being more prevalent in the elderly.
PubMed: 38736787
DOI: 10.4103/jfmpc.jfmpc_645_23 -
The Journal of Neuroscience : the... May 2022Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion...
Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson's disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioral modulation. Interestingly, while a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. A total of 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo. To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing. Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition. Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing. Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition. A high prevalence of emotion recognition difficulties among clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes. However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights. The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition. Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.
Topics: Adult; Dopamine; Dopamine D2 Receptor Antagonists; Emotions; Female; Haloperidol; Humans; Male; Perception
PubMed: 35501156
DOI: 10.1523/JNEUROSCI.2364-21.2022 -
Neuropharmacology Mar 2023Dysfunction of goal-directed behaviors under stressful or pathological conditions results in impaired decision-making and loss of flexibility of thoughts and behaviors,... (Review)
Review
Dysfunction of goal-directed behaviors under stressful or pathological conditions results in impaired decision-making and loss of flexibility of thoughts and behaviors, which underlie behavioral deficits ranging from depression, obsessive-compulsive disorders and drug addiction. Tackling the neuromodulators fine-tuning this core behavioral element may facilitate the development of effective strategies to control these deficits present in multiple psychiatric disorders. The current investigation of goal-directed behaviors has concentrated on dopamine and glutamate signaling in the corticostriatal pathway. In accordance with the beneficial effects of caffeine intake on mood and cognitive dysfunction, we now propose that caffeine's main site of action - adenosine A receptors (AR) - represent a novel target to homeostatically control goal-directed behavior and cognitive flexibility. AR are abundantly expressed in striatopallidal neurons and colocalize and interact with dopamine D2, NMDA and metabotropic glutamate 5 receptors to integrate dopamine and glutamate signaling. Specifically, striatopallidal AR (i) exert an overall "break" control of a variety of cognitive processes, making AR antagonists a novel strategy for improving goal-directed behavior; (ii) confer homeostatic control of goal-directed behavior by acting at multiple sites with often opposite effects, to enhance cognitive flexibility; (iii) integrate dopamine and adenosine signaling through multimeric AR-DR heterocomplexes allowing a temporally precise fine-tuning in response to local signaling changes. As the U.S. Food and Drug Administration recently approved the AR antagonist Nourianz® (istradefylline) to treat Parkinson's disease, striatal AR-mediated control of goal-directed behavior may offer a new and real opportunity for improving deficits of goal-directed behavior and enhance cognitive flexibility under various neuropsychiatric conditions. This article is part of the Special Issue on "Purinergic Signaling: 50 years".
Topics: Humans; Dopamine; Adenosine; Receptor, Adenosine A2A; Caffeine; Goals; Corpus Striatum; Glutamates; Cognition
PubMed: 36634866
DOI: 10.1016/j.neuropharm.2023.109421 -
Frontiers in Pharmacology 2023Despite advances in antiemetics and protocolized postoperative nausea vomiting (PONV) management, it remains one of the most common postoperative adverse events. In... (Review)
Review
Despite advances in antiemetics and protocolized postoperative nausea vomiting (PONV) management, it remains one of the most common postoperative adverse events. In patients who developed PONV despite antiemetic prophylaxis, giving a rescue treatment from the same class of medication is known to be of limited efficacy. Given the widespread use of 5-HT3 antagonists as PONV prophylaxis, another class of effective intravenous rescue antiemetic is in dire need, especially when prophylaxis fails, and rescue medication is utilized. Dopamine antagonists were widely used for the treatment of PONV but have fallen out of favor due to some of their side effect profiles. Amisulpride was first designed as an antipsychotic medication but was found to have antiemetic properties. Here we will review the historical perspective on the use of dopamine receptor antagonist antiemetics, as well as the evidence on the efficacy and safety of amisulpride.
PubMed: 38026950
DOI: 10.3389/fphar.2023.1274214 -
Reviews in the Neurosciences Aug 2020In this review, a series of experiments is presented, in which γ-amino butyric acid (GABA)ergic and glutamatergic effects on dopamine function in the rat nigrostriatal... (Review)
Review
In this review, a series of experiments is presented, in which γ-amino butyric acid (GABA)ergic and glutamatergic effects on dopamine function in the rat nigrostriatal and mesolimbic system was systematically assessed after pharmacological challenge with GABAA receptor (R) and and N-methyl d-aspartate (NMDA)R agonists and antagonists. In these studies, [123I]iodobenzamide binding to the D2/3R was mesured in nucleus accumbens (NAC), caudateputamen (CP), substantia nigra/ventral tegmental area (SN/VTA), frontal (FC), motor (MC) and parietal cortex (PC) as well as anterior (aHIPP) and posterior hippocampus (pHIPP) with small animal SPECT in baseline and after injection of either the GABAAR agonist muscimol (1 mg/kg), the GABAAR antagonist bicuculline (1 mg/kg), the NMDAR agonist d-cycloserine (20 mg/kg) or the NMDAR antagonist amantadine (40 mg/kg). Muscimol reduced D2/3R binding in NAC, CP, SN/VTA, THAL and pHIPP, while, after amantadine, decreases were confined to NAC, CP and THAL. In contrast, d-cycloserine elevated D2/3R binding in NAC, SN/VTA, THAL, frontal cortex, motor cortex, PC, aHIPP and pHIPP, while, after bicuculline, increases were confined to CP and THAL. Taken together, similar actions on regional dopamine levels were exterted by the GABAAR agonist and the NMDAR antagonist on the one side and by the GABAAR antagonist and the NMDAR agonist on the other, with agonistic action, however, affecting more brain regions. Thereby, network analysis suggests different roles of GABAARs and NMDARs in the mediation of nigrostriatal, nigrothalamocortical and mesolimbocortical dopamine function.
Topics: Animals; Bicuculline; Dopamine; Humans; Muscimol; Nucleus Accumbens; Rats; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate
PubMed: 32619197
DOI: 10.1515/revneuro-2019-0112 -
Pharmacological Research Nov 2020Dopamine is a member of the catecholamine family and is associated with multiple physiological functions. Together with its five receptor subtypes, dopamine is closely... (Review)
Review
Dopamine is a member of the catecholamine family and is associated with multiple physiological functions. Together with its five receptor subtypes, dopamine is closely linked to neurological disorders such as schizophrenia, Parkinson's disease, depression, attention deficit-hyperactivity, and restless leg syndrome. Unfortunately, several dopamine receptor-based agonists used to treat some of these diseases cause nausea and vomiting as impending side-effects. The high degree of cross interactions of dopamine receptor ligands with many other targets including G-protein coupled receptors, transporters, enzymes, and ion-channels, add to the complexity of discovering new targets for the treatment of nausea and vomiting. Using activation status of signaling cascades as mechanism-based biomarkers to foresee drug sensitivity combined with the development of dopamine receptor-based biased agonists may hold great promise and seems as the next step in drug development for the treatment of such multifactorial diseases. In this review, we update the present knowledge on dopamine and dopamine receptors and their potential roles in nausea and vomiting. The pre- and clinical evidence provided in this review supports the implication of both dopamine and dopamine receptor agonists in the incidence of emesis. Besides the conventional dopaminergic antiemetic drugs, potential novel antiemetic targeting emetic protein signaling cascades may offer superior selectivity profile and potency.
Topics: Animals; Antiemetics; Dopamine; Dopamine Agonists; Dopamine D2 Receptor Antagonists; Humans; Receptors, Dopamine D2; Receptors, Dopamine D3; Signal Transduction; Vomiting
PubMed: 32814171
DOI: 10.1016/j.phrs.2020.105124 -
Brain Research Bulletin Apr 2023Stress contributes to pain sensation by affecting several neural pathways, including mesolimbic-cortical dopamine neurons. Nucleus accumbens, an essential element of the...
Stress contributes to pain sensation by affecting several neural pathways, including mesolimbic-cortical dopamine neurons. Nucleus accumbens, an essential element of the mesolimbic dopaminergic pathway, plays a fundamental role in modulating pain and is differentially influenced by stressful events. Since we previously demonstrated the marked association of intra-NAc dopamine receptors with forced swim stress-evoked analgesia in acute pain state, this research was conducted to consider the contribution of intra-accumbal D1- and D2-like dopamine receptors to modulating effects of exposure to restraint stress in pain-related behaviors during the tail-flick test. Stereotaxic surgery was executed to implant a guide cannula within the NAc in male Wistar rats. On the test day, different concentrations of SCH23390 and Sulpiride as D1- and D2-like dopamine receptor antagonists, respectively, were unilaterally microinjected within the NAc. The vehicle animals received saline or 12 % DMSO (0.5 µl) instead of SCH23390 or Sulpiride into the NAc, respectively. Five minutes following receiving drug or vehicle, animals were restrained for 3 h and then their acute nociceptive threshold was measured for a 60-min period by the tail-flick test. Our data revealed that RS considerably enhanced antinociceptive reaction in acute pain states. The analgesia evoked by RS dramatically declined following blocking either D1- or D2-like dopamine receptors in the NAc, an effect was more noticeable by D1-like dopamine receptor antagonist. These findings indicated that intra-NAc dopamine receptors are considerably mediated in the RS-produced analgesia in acute pain states, suggesting their possible role in psychological stress and disease.
Topics: Rats; Animals; Male; Sulpiride; Rats, Wistar; Acute Pain; Receptors, Dopamine D2; Receptors, Dopamine D1; Dopamine Antagonists; Nucleus Accumbens; Analgesics
PubMed: 36889361
DOI: 10.1016/j.brainresbull.2023.03.003 -
Cell Reports Sep 2022Low dopamine D2 receptor (D2R) availability in the striatum can predispose for cocaine abuse; though how low striatal D2Rs facilitate cocaine reward is unclear....
Low dopamine D2 receptor (D2R) availability in the striatum can predispose for cocaine abuse; though how low striatal D2Rs facilitate cocaine reward is unclear. Overexpression of D2Rs in striatal neurons or activation of D2Rs by acute cocaine suppresses striatal Penk mRNA. Conversely, low D2Rs in D2-striatal neurons increases striatal Penk mRNA and enkephalin peptide tone, an endogenous mu-opioid agonist. In brain slices, met-enkephalin and inhibition of enkephalin catabolism suppresses intra-striatal GABA transmission. Pairing cocaine with intra-accumbens met-enkephalin during place conditioning facilitates acquisition of preference, while mu-opioid receptor antagonist blocks preference in wild-type mice. We propose that heightened striatal enkephalin potentiates cocaine reward by suppressing intra-striatal GABA to enhance striatal output. Surprisingly, a mu-opioid receptor antagonist does not block cocaine preference in mice with low striatal D2Rs, implicating other opioid receptors. The bidirectional regulation of enkephalin by D2R activity and cocaine offers insights into mechanisms underlying the vulnerability for cocaine abuse.
Topics: Analgesics, Opioid; Animals; Cocaine; Cocaine-Related Disorders; Corpus Striatum; Enkephalin, Methionine; Enkephalins; Mice; Narcotic Antagonists; RNA, Messenger; Receptors, Dopamine D1; Receptors, Dopamine D2; Reward; gamma-Aminobutyric Acid
PubMed: 36170833
DOI: 10.1016/j.celrep.2022.111440 -
Drug Design, Development and Therapy 2023This review aims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of... (Review)
Review
This review aims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of schizophrenia. Lurasidone has antagonistic effects on the dopamine D, 5-hydroxytryptamine (5-HT), and 5-HT receptors and a partial agonistic effect on the 5-HT receptor with low affinities for muscarinic M, histamine H, and a adrenergic receptors. The receptor-binding profile of lurasidone is thought to be associated with fewer side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Behavioral pharmacological studies have demonstrated that lurasidone exerts anxiolytic and antidepressive effects and improves cognitive function, which are associated with the modulation of 5-HT and 5-HT receptors. Literature search using PubMed was performed to find published studies of randomized controlled trials and recent meta-analyses regarding efficacy and safety, particularly metabolic side effects of lurasidone in schizophrenia. In short-term studies, the results of randomized placebo-controlled trials and meta-analyses have suggested that lurasidone was superior to placebo in improving total psychopathology, positive symptoms, negative symptoms, and general psychopathology in patients with acute schizophrenia. Regarding safety, lurasidone had minimal metabolic side effects, and was identified as one of the drugs with the most benign profiles for metabolic side effects. Long-term trials revealed that lurasidone had the preventive effects on relapse, with minimal effects on weight gain and other metabolic side effects. Furthermore, lurasidone improves cognitive and functional performance of patients with schizophrenia, especially in long-term treatment. Patients with schizophrenia require long-term treatment with antipsychotics for relapse prevention; thus, minimizing weight gain and other side effects is crucial. Lurasidone is suitable as one of the first-line antipsychotic drugs in the acute phase, and a switching strategy should be considered during the maintenance phase, to balance efficacy and adverse effects and achieve favorable outcomes in the long-term course of schizophrenia.
Topics: Humans; Lurasidone Hydrochloride; Schizophrenia; Serotonin; Isoindoles; Thiazoles; Antipsychotic Agents; Weight Gain
PubMed: 37789971
DOI: 10.2147/DDDT.S366769 -
Journal of Neurochemistry Mar 2022Striatal dopamine release is key for learning and motivation and is composed of subregions including the dorsal striatum (DS), nucleus accumbens core, and the nucleus...
Striatal dopamine release is key for learning and motivation and is composed of subregions including the dorsal striatum (DS), nucleus accumbens core, and the nucleus accumbens shell. Spontaneously occurring dopamine release was compared across these subregions. Dopamine release/uptake dynamics differ across striatal subregions, with dopamine transient release amplitude and release frequency greatest in male mice, and the largest signals observed in the DS. Surprisingly, female mice exhibited little regional differences in dopamine release for DS and nucleus accumbens core regions, but lower release in the nucleus accumbens shell. Blocking voltage-gated K channel (Kv channels) with 4-aminopyridine enhanced dopamine detection without affecting reuptake. The 4-aminopyridine effects were greatest in ventral regions of female mice, suggesting regional differences in Kv channel expression. The dopamine transporter blocker cocaine also enhanced detection across subregions in both sexes, with greater overall increased release in females than males. Thus, sex differences in dopamine transmission are apparent and likely include differences in the Kv channel and dopamine transporter function. The lack of regional differences in dopamine release observed in females indicates differential regulation of spontaneous and evoked dopamine release.
Topics: 4-Aminopyridine; Animals; Cocaine; Corpus Striatum; Dopamine; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins; Female; Male; Mice; Nucleus Accumbens; Sex Characteristics
PubMed: 34265080
DOI: 10.1111/jnc.15473