Effects of D2 dopamine receptor antagonists on fos protein expression in the striatal complex and entorhinal cortex of the nonhuman primate

Antipsychotic Drug Effects in Schizophrenia: A Review of Longitudinal fMRI Investigations and Neural Interpretations

“…[72,76]). In contrast, acute exposure to haloperidol leads to similar increases in expression in striatum [72,[74][75][76] but does not lead to increased Fos expression in neocortical regions [67,70,71]. Similar findings have been reported in striatum for other IEGs including activity regulated cytoskeletal protein (Arc) mRNA [77,78], zif268 [76], and Homer1a [79].…”

“…Measurement of FosB or c-Fos has been successfully employed to distinguish the effects of typical and atypical antipsychotics. Acute exposure to clozapine or olanzapine leads to increased expression of FosB or c-Fos in retrosplenial cortex [67], locus coeruleus [68,69], PFC [69][70][71][72][73], and striatum [73][74][75] (but see refs. [72,76]).…”

Dopamine D2‐like antagonists induce chromatin remodeling in striatal neurons through cyclic AMP‐protein kinase A and NMDA receptor signaling

“…Co-regulation of H3 phospho-acetylation and early response genes The kinetics of striatal H3 phospho-acetylation bears resemblance to the surge of early response proteins after activation of D1 or blockade of D 2 -like receptors (Dragunow et al 1990;Graybiel et al 1990;Robertson et al 1992;Deutch et al 1996;Gerfen et al 1998;Missale et al 1998). Considering that the dual histone modification, H3pS10-acK14, defines open chromatin and activation of gene expression in yeast, mammals and Drosophila (Cheung et al 2000;Clayton et al 2000;Lo et al 2000;Thomson et al 2001), its coordinated regulation in concert with immediate-early transcription factors, including fos (Curran and Morgan 1995), makes biological sense; levels of c-fos protein in striatum and global levels of H3pS10-acK14 in striatal chromatin are transiently increased after acute treatment and may operate synergistically to enhance transcription of selected genes.…”

“…We find that, in vivo, D 2 -like antagonistinduced H3 phospho-acetylation is inhibited by the NMDA receptor antagonist MK-801 and by the protein kinase A (PKA) inhibitor Rp-adenosine 3c¢,5c¢-cyclic monophosphorothioate triethylammonium salt but increased by the PKA activator Sp-adenosine 3c¢,5c¢-cyclic monophosphorothioate triethylammonium salt. Furthermore, in dissociated striatal cultures which lack midbrain and cortical pre-synaptic inputs, H3 phospho-acetylation was induced by glutamate, L- Robertson et al 1991;Nguyen et al 1992;Deutch et al 1996) followed by increased transcription of neuropeptides, second and third messenger molecules, receptors, ion channels and other neurotransmission-related molecules (Merchant and Dorsa 1993;Fox et al 1994;Delfs et al 1995;Fitzgerald et al 1995;Laprade and Soghomonian 1995;Schoots et al 1995;Doucet et al 1996;Moratalla et al 1996;Eastwood et al 1997;Healy and Meador-Woodruff 1997;Mijnster et al 1998; Atkins et al Abbreviations used: cAMP-PKA, cAMP-dependent protein kinase A; Rp-cAMPs, Rp-Adenosine 3c¢,5c¢-cyclic monophosphorothioate triethylammonium salt; Sp-cAMPs, Sp-Adenosine 3c¢,5c¢-cyclic monophosphorothioate triethylammonium salt. …”

“…The molecular cascades linking blockade of D 2 -like receptors to reduction of psychosis are unknown but transcriptional mechanisms appear to be involved (Robertson et al 1992;Gunther et al 2003). Upon inhibition of D 2 -like signaling, striatal and pallidal gene expression is altered in an orchestrated and sequential fashion, starting with the transient expression of early response genes (Dragunow et al 1990;Robertson et al 1991;Nguyen et al 1992;Deutch et al 1996) followed by increased transcription of neuropeptides, second and third messenger molecules, receptors, ion channels and other neurotransmission-related molecules (Merchant and Dorsa 1993;Fox et al 1994;Delfs et al 1995;Fitzgerald et al 1995;Laprade and Soghomonian 1995;Schoots et al 1995;Doucet et al 1996;Moratalla et al 1996;Eastwood et al 1997;Healy and Meador-Woodruff 1997;Mijnster et al 1998;Atkins et al 1999;Nakahara et al 2001;Chong et al 2002;Lau et al 2003;Lipska et al 2003;McCullumsmith et al 2003).…”