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D 2 but not D 3 receptors are elevated after 9 or 11 months chronic haloperidol treatment: Influence of withdrawal period
Author(s) -
Joyce Jeffrey N.
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1035
Subject(s) - haloperidol , olfactory tubercle , dopamine receptor d2 , receptor , dopamine receptor d3 , medicine , endocrinology , nucleus accumbens , chemistry , dopamine
Abstract Previous postmortem studies have identified divergent alterations in D 2 and D 3 receptors in schizophrenia but those results cannot be interpreted without further understanding of whether antipsychotic regulation of the D 3 receptor is different from that of the D 2 receptor. Depot parenteral administration of haloperidol decanoate was utilized to achieve consistent high levels in rat brain for 9 months with 2‐month withdrawal or 11 months with 48‐h withdrawal and compared to vehicle control and acute haloperidol (48‐h) treatment groups. Autoradiographic means for measuring levels of D 2 ([ 3 H]‐spiperone) and D 3 receptors ([ 125 I] trans 7‐OH‐PIPAT) and of D 3 mRNA by in situ hybridization histochemistry in rat caudate‐putamen, nucleus accumbens, islands of Calleja, and olfactory tubercle determined that there were significant group differences for regulation of D 2 receptor. Chronic haloperidol for 9 or 11 months elevated D 2 but not D 3 receptors or D 3 mRNA in all regions measured. Acute haloperidol treatment had no significant effects for any measure. Treatment for 9 months with a 2‐month withdrawal resulted in a persistent increase in D 2 receptors that was greater than that observed in the 11 months with 48‐h withdrawal. This effect was most noticeable in the olfactory tubercle. These data confirm previous findings that short‐ or long‐term haloperidol treatment leads to elevations in D 2 but not D 3 receptors or D 3 mRNA, and long‐term withdrawal from chronic haloperidol does not lead to elevations in D 3 receptors or D 3 mRNA. This suggests that an elevation in D 3 receptors identified at postmortem in schizophrenics withdrawn from antipsychotics is not the result of the previous drug history [Gurevich et al. (1997) Arch Gen Psychiatry 54:225–232]. Synapse 40:137–144, 2001. © 2001 Wiley‐Liss, Inc.