Rapid Changes in D1 and D2 Dopamine Receptor Binding in Striatal Subregions after a Single Dose of Phencyclidine

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 [3H] SCH 23390 and [3H] 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.

Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder.

Abnormal cholinergic neurotransmission has been suggested to occur in psychiatric illness. Therefore, this study investigated cholinergic muscarinic receptors in the anterior cingulate cortex (ACC) of schizophrenia, bipolar disorder and major depression disorder (n=15 per group). We used quantitative autoradiography to measure [(3)H]pirenzepine binding to M1 and M4 receptors. Brain tissue was obtained from the Stanley Foundation Neuropathology Consortium. [(3)H]pirenzepine binding was higher in superficial laminae (I-II) than in deep laminae (III-VI) of the ACC. There was a significant 24% reduction in the density of [(3)H]pirenzepine in the deep laminae and a significant 19% reduction in the upper laminae of the ACC in the schizophrenia group compared to the control group. There were no differences in [(3)H]pirenzepine binding in any laminae of the ACC in the bipolar or major depression groups compared with the control group, except for a trend towards decreased [(3)H]pirenzepine binding in subjects with major depression relative to control subjects. We also detected a significant effect of suicide on [(3)H]pirenzepine binding in the ACC in subjects who died as a result of suicide relative to those who did not, which was more evident in patients with schizophrenia. A significant effect of the onset of the disease was also observed that was more evident in patients with bipolar disorder. The study provides evidence of decreased muscarinic receptor density in the ACC in schizophrenia but no evidence for significant changes in these receptors in the bipolar and major depression groups. The changes observed in schizophrenia may contribute to dysfunctional ACC neural circuits.