title: Effects of neurotensin gene knockout in mice on the behavioral effects of cocaine.
abstract: BACKGROUND
  The neuropeptide neurotensin (NT), which has been implicated in the modulation of dopamine signaling, is expressed in a subset of dopamine neurons and antagonism of the NT receptor has been reported to reduce psychostimulant-induced behavior. Gene knockout (KO) of the neurotensin/neuromedin N precursor provides an approach to delineating possible roles of endogenous NT in psychostimulant-induced responses.
  
  
  OBJECTIVE
  Involvement of NT in cocaine responses was examined by comparing acute and conditioned locomotor responses, conditioned place preference, and sensitization in wild-type (WT), heterozygous, and homozygous NT KO mice.
  
  
  RESULTS
  NT KO mice did not differ from their WT or heterozygous littermates in either baseline or acute cocaine-stimulated locomotor activity. The locomotor stimulant effects of cocaine were slightly prolonged in these mice under some, but not all, experimental conditions. The rewarding effects of cocaine as assessed in the conditioned place preference and conditioned locomotion paradigms were also similar between genotypes at all cocaine doses tested.
  
  
  CONCLUSIONS
  These results suggest that endogenous NT is not involved in cocaine-mediated behaviors in most circumstances, but under some conditions, a slight prolongation of the effects of cocaine was observed in the absence of endogenous NT.
authors: Molecular Neurobiology Branch, National Institute on Drug Abuse, NIH/DHHS, 333 Cassell Drive, Baltimore, MD 21224, USA. shall@intra.nida.nih.gov
authors: F Scott
authors: FS
authors: Hall
authors: Marjorie
authors: M
authors: Centeno
authors: Maria T G
authors: MT
authors: Perona
authors: Jordan
authors: J
authors: Adair
authors: Paul R
authors: PR
authors: Dobner
authors: George R
authors: GR
authors: Uhl
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009496:Neurotensin / Q000172:deficiency* / Q000235:genetics
chemical_list: D009496:Neurotensin; D003042:Cocaine