Neurotensin gene expression and behavioral responses following administration of psychostimulants and antipsychotic drugs in dopamine D-3 receptor deficient mice

Exposure to psychostimulants and antipsychotics increases neurotensin (NT)g ene expression in the striatum and nucleus accumbens. To investigate the co ntribution of D-3 receptors to these effects toe used mice with targeted di sruption of the D-3 receptor gene. Basal NT mRNA expression was similar in D-3 receptor mutant mice and wild-type animals. Acute administration of hal operidol increased NT gene expression in the striatum in D-3 +/+, D-3 +/- a nd D-3 -/- mice. Similarly, acute cocaine and amphetamine induced NT mRNA e xpression in the nucleus accumbens shell and olfactory tubercle to a compar able extent in D-3 mutants and wild-type mice. Daily injection of cocaine f or seven days increased NT mRNA in it restricted population of neurons in t he dorsomedial caudal striatum of D-3 +/+ mice, but not in D-3 -/- and D-3 +/- animals. No differences were observed between D-3 receptor mutant mice and wild-type littermates in the locomotor activity and stereotyped behavio rs induced by repeated cocaine administration. These findings demonstrate t hat dopamine D-3 receptors are not necessary for the acute NT mRNA response to drugs of abuse and antipsychotics but appear to play a role in the regu lation of NT gene induction in striatal neurons after repented cocaine. In addition, ota results indicate that the acute locomotor response to cocaine and development of psychostimulant-induced behavioral sensitization do not require functional D-3 receptors. [Neuropsychopharmacology 24:170-182, 200 1] (C) 2000 American College of Neuropsychopharmacology. Published by Elsev ier Science Inc.