Dopamine D2-receptor mRNA level in rat striatum after chronic haloperidol treatment

Abstract

Chronic treatment with haloperidol, a D2-receptor antagonist and a neuroleptic, increases the number of D2-receptors in rat striatum. However, there have been inconsistent reports on the D2-receptor mRNA level, one showing the increase in the mRNA level and another detecting no changes. Furthermore, they did not distinguish the two isoforms of D2-receptor, D2A and D2B. In the present work, both D2- and DeA-receptor mRNA levels in rat striatum were estimated after chronic administration of haloperidol. There was, within the sensitivity of the assay, no significant increase in either of them between 3 and 24 h after the last administration. This suggests that chronic haloperidol treatment does not affect the transcriptional regulation of the D2-receptor gene or the alternative splicing process of its transcripts.

D2 but not D3 receptors are elevated after 9 or 11 months chronic haloperidol treatment: Influence of withdrawal period

“…The concentration of [ 3 H]-spiperone used in this study is approximately 7 times the K d for the D 2 receptor and, thus, the elevations in concentrations of sites accurately reflects B max values. While we did not examine D 2 mRNA levels in this study, previous studies have demonstrated that the increase in D 2 receptor number does not always lead to an elevation in D 2 mRNA (Creese et al, 1992;Fox et al, 1994;Matsunaga et al, 1991), although higher doses and more prolonged exposure does elevate D 2 mRNA (D' Souza et al, 1997;Damask et al, 1996;Egan et al, 1994;Lévesque et al, 1995;Rogue et al, 1991). It is likely that a change in posttranslational processing of D 2 receptors also contributes to elevated numbers (Pich et al, 1987).…”

The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

“…In rat pituitary, 21 days of haloperidol upregulated D2 mRNA expression [24]. Although early striatal studies were negative in rodents [25–27], subsequent studies found upregulated striatal D2 mRNA expression changes after chronic haloperidol treatment [23, 28–32]. Four-week administration upregulated striatal and prefrontal cortical Drd2 expression in rats [22, 32].…”

Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [11C]MP-10 PET rodent imaging study with ex vivo confirmation

“…Dopamine D 2 receptor mRNA upregulation has previously been reported to be changed by chronic haloperidol treatment, although reports are mixed. 18,19,31 The lack of dopamine D 2 receptor mRNA may suggest that high and sustained levels of D 2 receptor blockade may not have been achieved but high levels of drug in plasma, increased levels of Nts mRNA and high vacuous chewing movement scores in the haloperidol group are indicators of high and sustained D 2 receptor blockade. We did not find any change in Pde10a, Pde1b or D 2 receptor mRNA levels in the striatum after chronic haloperidol treatment; however, we observed a highly significant increase in the striatal Nts mRNA levels indicating transcriptional activation due to antipsychotic treatment.…”

“…mRNA levels of four target genes ( Pde10a , Pde1b , dopamine D 2 receptor and neurotensin ) were chosen as changes in expression of these genes due to chronic antipsychotic treatment have been reported. 7,18,19 Western blotting was carried out to quantify striatal protein levels. Total and PDE10A-specific cAMP PDE activity in striatum were measured in enzymatic assays to assess potential changes in PDE activity of PDE10A or other PDEs.…”