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Rapid changes in d1 and d2 dopamine receptor binding in striatal subregions after a single dose of phencyclidine.

Dalton VS, Zavitsanou K - Clin Psychopharmacol Neurosci (2011)

Bottom Line: In vitro autoradiography was carried out using [(3)H] SCH 23390 and [(3)H] raclopride that target D1R and D2R respectively, in cryostat brain sections.Two way analysis of variance (ANOVA), revealed an overall effect of PCP treatment (F [1,63]=9.065; p=0.004) on D1R binding with an 18% decrease (p<0.01) in binding in the medial caudate putamen.PCP treatment also had an overall effect on D2R binding (F [1,47]=5.450; p=0.024) and a trend for an increase in D2R binding across all the brain regions examined.

View Article: PubMed Central - PubMed

Affiliation: Schizophrenia Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, Australia. ; ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Sydney, Australia.

ABSTRACT

Objective: In humans, a single exposure to phencyclidine (PCP) can induce a schizophrenia-like psychosis which can persist for up to two weeks. In rats, an acute dose of PCP increases dopaminergic activity and causes changes in dopamine related behaviours some of which are sexually dimorphic. To better understand the effects of PCP on dopamine receptor adaptations in the short term we examined dopamine D1-like receptors (D1R) and D2-like receptors (D2R) in the mesolimbic and nigrostriatal dopamine pathways, 4 hours after exposure to PCP in female rats.

Methods: Animals received a single dose of 40 mg/kg PCP and were sacrificed 4 hours later. In vitro autoradiography was carried out using [(3)H] SCH 23390 and [(3)H] raclopride that target D1R and D2R respectively, in cryostat brain sections.

Results: Two way analysis of variance (ANOVA), revealed an overall effect of PCP treatment (F [1,63]=9.065; p=0.004) on D1R binding with an 18% decrease (p<0.01) in binding in the medial caudate putamen. PCP treatment also had an overall effect on D2R binding (F [1,47]=5.450; p=0.024) and a trend for an increase in D2R binding across all the brain regions examined.

Conclusion: These results suggest opposing D1R and D2R adaptations in striatal subregions of female rats following acute exposure to PCP that may occur through indirect mechanisms.

No MeSH data available.


Related in: MedlinePlus

Typical autoradiographs showing binding of the D1 and D2 receptor ligands, [3H] SCH 23390 and [3H] raclopride respectively in control and PCP treated female rats. Line diagram showing brain regions is adapted from Paxinos and Watson (1997). PCP, phencyclidine; ACB, nucleus accumbens; CPUL, lateral caudate putamen; CPUM, medial caudate putamen; TU, olfactory tubercle nucleus.
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Figure 1: Typical autoradiographs showing binding of the D1 and D2 receptor ligands, [3H] SCH 23390 and [3H] raclopride respectively in control and PCP treated female rats. Line diagram showing brain regions is adapted from Paxinos and Watson (1997). PCP, phencyclidine; ACB, nucleus accumbens; CPUL, lateral caudate putamen; CPUM, medial caudate putamen; TU, olfactory tubercle nucleus.

Mentions: All films were analyzed by using a computer-assisted image analysis system, Multi-Analyst, connected to a GS-690 Imaging Densitometer (Bio-Rad, USA). As detailed in Fig. 1, brain regions quantified included the lateral and medial caudate putamen, nucleus accumbens and the olfactory tubercle. [3H] SCH 23390 binding was also quantified in the substantia nigra (Fig. 2). Quantification of receptor binding in each brain region was performed by measuring the average optical density in six adjacent brain sections (three for the total binding and three for the non-specific binding). Non-specific binding was subtracted from the total binding to determine the specific binding. Optical density measurements for specific binding were then converted into fmoles [3H] SCH 23390 or [3H] raclopride per mg tissue equivalent (fmol/mg TE), according to the calibration curve obtained from the tritium standards.


Rapid changes in d1 and d2 dopamine receptor binding in striatal subregions after a single dose of phencyclidine.

Dalton VS, Zavitsanou K - Clin Psychopharmacol Neurosci (2011)

Typical autoradiographs showing binding of the D1 and D2 receptor ligands, [3H] SCH 23390 and [3H] raclopride respectively in control and PCP treated female rats. Line diagram showing brain regions is adapted from Paxinos and Watson (1997). PCP, phencyclidine; ACB, nucleus accumbens; CPUL, lateral caudate putamen; CPUM, medial caudate putamen; TU, olfactory tubercle nucleus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569081&req=5

Figure 1: Typical autoradiographs showing binding of the D1 and D2 receptor ligands, [3H] SCH 23390 and [3H] raclopride respectively in control and PCP treated female rats. Line diagram showing brain regions is adapted from Paxinos and Watson (1997). PCP, phencyclidine; ACB, nucleus accumbens; CPUL, lateral caudate putamen; CPUM, medial caudate putamen; TU, olfactory tubercle nucleus.
Mentions: All films were analyzed by using a computer-assisted image analysis system, Multi-Analyst, connected to a GS-690 Imaging Densitometer (Bio-Rad, USA). As detailed in Fig. 1, brain regions quantified included the lateral and medial caudate putamen, nucleus accumbens and the olfactory tubercle. [3H] SCH 23390 binding was also quantified in the substantia nigra (Fig. 2). Quantification of receptor binding in each brain region was performed by measuring the average optical density in six adjacent brain sections (three for the total binding and three for the non-specific binding). Non-specific binding was subtracted from the total binding to determine the specific binding. Optical density measurements for specific binding were then converted into fmoles [3H] SCH 23390 or [3H] raclopride per mg tissue equivalent (fmol/mg TE), according to the calibration curve obtained from the tritium standards.

Bottom Line: In vitro autoradiography was carried out using [(3)H] SCH 23390 and [(3)H] raclopride that target D1R and D2R respectively, in cryostat brain sections.Two way analysis of variance (ANOVA), revealed an overall effect of PCP treatment (F [1,63]=9.065; p=0.004) on D1R binding with an 18% decrease (p<0.01) in binding in the medial caudate putamen.PCP treatment also had an overall effect on D2R binding (F [1,47]=5.450; p=0.024) and a trend for an increase in D2R binding across all the brain regions examined.

View Article: PubMed Central - PubMed

Affiliation: Schizophrenia Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, Australia. ; ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Sydney, Australia.

ABSTRACT

Objective: In humans, a single exposure to phencyclidine (PCP) can induce a schizophrenia-like psychosis which can persist for up to two weeks. In rats, an acute dose of PCP increases dopaminergic activity and causes changes in dopamine related behaviours some of which are sexually dimorphic. To better understand the effects of PCP on dopamine receptor adaptations in the short term we examined dopamine D1-like receptors (D1R) and D2-like receptors (D2R) in the mesolimbic and nigrostriatal dopamine pathways, 4 hours after exposure to PCP in female rats.

Methods: Animals received a single dose of 40 mg/kg PCP and were sacrificed 4 hours later. In vitro autoradiography was carried out using [(3)H] SCH 23390 and [(3)H] raclopride that target D1R and D2R respectively, in cryostat brain sections.

Results: Two way analysis of variance (ANOVA), revealed an overall effect of PCP treatment (F [1,63]=9.065; p=0.004) on D1R binding with an 18% decrease (p<0.01) in binding in the medial caudate putamen. PCP treatment also had an overall effect on D2R binding (F [1,47]=5.450; p=0.024) and a trend for an increase in D2R binding across all the brain regions examined.

Conclusion: These results suggest opposing D1R and D2R adaptations in striatal subregions of female rats following acute exposure to PCP that may occur through indirect mechanisms.

No MeSH data available.


Related in: MedlinePlus