Amphetamine-elicited striatal Fos expression is attenuated in neurotensin null mutant mice.
Neurotensin (NT) has been suggested to interact with dopamine systems in different forebrain sites to exert both antipsychotic- and psychostimulant-like effects. We previously found that genetic or pharmacological manipulations that disrupt endogenous NT signaling attenuate antipsychotic drug-induced Fos expression in the dorsolateral and central striatum but not other striatal regions. To assess the role of NT in psychostimulant responses, we examined the ability of d-amphetamine (AMP) to induce Fos in wild-type and NT null mutant mice. AMP-elicited Fos expression was significantly attenuated in the medial striatum of NT null mutant mice, but was unaffected in other striatal territories. Similar results were obtained in rats and mice pretreated with the high affinity neurotensin receptor (NTR1) antagonist SR 48692. The effect of the NTR1 antagonist was particularly apparent in the striatal patch (striosome) compartment, as defined by mu-opioid receptor immunoreactivity. These data suggest that NT is required for the full activation by AMP of medial striatal neurons.
Fadel
Jim
J
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA. jrfadel@med.sc.edu
Dobner
Paul R
PR
Deutch
Ariel Y
AY
D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009496:Neurotensin / Q000235:genetics*; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D016761:Oncogene Proteins v-fos; D011720:Pyrazoles; D011804:Quinolines; C079087:SR 48692; D009496:Neurotensin; D000661:Amphetamine