Chronic administration of the histamine H3 receptor agonist immepip decreases l-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats

Immunomodulatory Effects of Dopamine in Inflammatory Diseases

“…Chronic administration of the histamine H3 receptor agonist immepip decreases L-Dopa-induced dyskinesias (28), while a combination of D2 agonists and inhibitors of endocannabinoid degradation improves parkinsonian motor deficits (131).…”

Role of the Dopaminergic System in the Striatum and Its Association With Functional Recovery or Rehabilitation After Brain Injury

“…Therefore, brain injury results in disruption of the connectivity of the corticostriatal, corticohypothalamic, corticopontocerebellar, and cerebellothalamocortical pathways ( Leergaard, 2003 ; Daskalakis et al, 2004 ; Shepherd, 2013 ). Other neural groups, such as the dopaminergic, noradrenergic, histaminergic and serotonergic systems, are altered by local axonal injury in brain contusions and direct mechanical injury ( Bueno-Nava et al, 2008 , 2010b ; Eakin et al, 2013 ; Jenkins et al, 2016 , 2018 ; Avila-Luna et al, 2019 ; Liao et al, 2019 ; Dougherty et al, 2020 ).…”

“…The classic model of basal ganglia function ( Figure 1A ) suggests that glutamatergic corticostriatal projections are critical for the activity of striatonigral and striatopallidal MSNs that form the direct and indirect pathways in the basal ganglia, respectively ( Albin et al, 1989 ). Alterations in dopaminergic function in the striatum are associated with motor disability, such as that observed in individuals with Parkinson’s disease and levodopa-induced dyskinesia ( Calabresi et al, 2014 ; Bastide et al, 2015 ; Fundament et al, 2016 ; Schonfeld et al, 2017 ; Avila-Luna et al, 2019 ). Therefore, some components of TBI pathophysiology likely have a basis in striatal dopaminergic dysfunction based on clinical and experimental evidence obtained from the basal ganglia, particularly the dorsal striatum ( Figure 1B ; Donnemiller et al, 2000 ; Costa et al, 2006 ; Yan et al, 2007 ; Bales et al, 2009 , 2011 ; Van Bregt et al, 2012 ; Osier and Dixon, 2016a ; Karelina et al, 2017 ; Treble-Barna et al, 2017 ; Jenkins et al, 2018 ; Jolly et al, 2019 ).…”

“…In the striatum, MSN heteroreceptors are localized in the cell membrane, including DA receptors (D 1 Rs and D 2 Rs), histamine receptors (H 3 Rs), muscarinic receptors (M1 and M4), adenosine receptors (A 1 Rs and A 2 A Rs), cannabinoid receptors (CB 1 Rs), metabotropic glutamate receptors (mGlu 1 / 5 Rs), and ionotropic glutamate receptors [ N -methyl- D -aspartic acid (NMDA) receptors, NMDARs] ( Jones et al, 2001 ; Meschler and Howlett, 2001 ; Kreitzer and Malenka, 2008 ; Bolam and Ellender, 2016 ; Rapanelli, 2017 ). As mentioned above with regard to the role of DA after TBI and during functional recovery, studies have shown that functional interactions exist between DA receptors and other heteroreceptors localized in MSNs of the striatum, such as D 1 R/A 1 R ( Fuxe et al, 2008 , 2010 ), D 1 R/D 3 R/A 1 R ( Fuxe et al, 2008 ), D 1 R/D 3 R ( Fuxe et al, 2008 ; Marcellino et al, 2008 ), D 1 R/H 3 R ( Garcia et al, 1997 ; Ferrada et al, 2009 ; Moreno et al, 2011 ; Avila-Luna et al, 2019 ), D 2 R/A 2 A R ( Fuxe et al, 2008 , 2010 ; Ferré et al, 2016 ; Ferré and Ciruela, 2019 ), D 2 R/H 3 R ( Humbert-Claude et al, 2007 ; Ferrada et al, 2008 ; Rapanelli et al, 2016 ; Rapanelli, 2017 ), D 2 R/A 2 A R/mGlu5R ( Fuxe et al, 2008 , 2010 ), D 2 R/NMDA ( Fuxe et al, 2008 ), D 2 R/CB 1 R ( Fuxe et al, 2008 ), and D 2 R/CB 1 R/A 2 A R ( Meschler and Howlett, 2001 ; Fuxe et al, 2008 , 2010 ) interactions (see Figure 3 ). Most of these functional interactions regulate neuronal activity via the adenylyl cyclase-mediated response in MSNs from both direct and indirect pathways of the basal ganglia (see Figure 3 ), but other interactions, such as D 2 R/NMDAR interactions, are associated with modulation of transmembrane ion currents ( Fuxe et al, 2008 ).…”

“…At the postsynaptic level, H 3 R activation inhibits D 1 R-induced cAMP formation in rat striatal slices ( Sanchez-Lemus and Arias-Montano, 2004 ), and D 1 Rs play a permissive role in H 3 R-mediated activation of mitogen-activated protein kinases (MAPKs) ( Moreno et al, 2011 ). At the motor behavior level, chronic H 3 R activation reduces dyskinesias induced by L -Dopa ( L -3,4-dihydroxyphenylalanine) in rats with 6-hydroxydopamine-induced lesions ( Avila-Luna et al, 2019 ). All of the functional interactions mentioned above may have important implications for future research on TBI and its treatment.…”