Differences in the regional and cellular localization of c-fos messenger RNA induced by amphetamine, cocaine and caffeine in the rat

Neuroscience. 1994 Apr;59(4):837-49. doi: 10.1016/0306-4522(94)90288-7.


Male rats were treated i.p. with either 5 mg/kg amphetamine, 3 and 30 mg/kg cocaine or 100 mg/kg caffeine and killed after 30 min. Brains were sectioned and processed for radioactive in situ hybridization histochemistry for the labelling of either c-fos, enkephalin, substance P, neurokinin B, choline acetyltransferase, somatostatin or adenosine A2A receptor messenger RNA. The distribution of c-fos messenger RNA was investigated both at the regional level using film autoradiography, and at the cellular level using emulsion autoradiography. All drug treatments except 3 mg/kg cocaine induced an increased level of c-fos messenger RNA in cells that had a neuron-like morphology. The cells that contained the c-fos messenger RNA were identified by making pairs of 5-microns sections in which one section was processed for c-fos messenger RNA and the other was processed for one of the other messenger RNA species. After amphetamine treatment, only some 10% of the cells in the striatum were labelled, and to a variable extent. Instead there was prominent labelling of a band in the cortex that runs parallel to the cortical surface. There was also a moderate degree of labelling in the nucleus accumbens. c-fos-positive cells were substance P-positive and negative for enkephalin or A2A receptor messenger RNA. Cocaine (30 mg/kg) induced a modest labelling in the caudate-putamen, as well as in the accumbens. With cocaine treatment (30 mg/kg), about 30% of striatal neuron-like cells were c-fos labelled. Most c-fos-positive cells were substance P-positive, but none of the c-fos-positive cells were enkephalin-positive or A2A-receptor-positive. Cocaine (3 mg/kg) had no significant effect on c-fos. Caffeine gave rise to a strong hybridization signal in the caudate-putamen, particularly the dorsolateral part. No other region examined differed significantly from control. With caffeine treatment, about 73% of neuron-like cells were c-fos labelled in the lateral striatum, but labelling was much less pronounced in the medial part or in the accumbens. c-fos-labelled cells were found in enkephalin-positive and enkephalin-negative, substance P-positive and substance P-negative, neurokinin B-positive and neurokinin B-negative groups. No choline acetyltransferase-positive or somatostatin-positive cells were found that were also c-fos-positive with any of the treatments. We conclude that each of the different CNS stimulant drugs induces a highly specific pattern of c-fos messenger RNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Biomarkers
  • Brain / drug effects*
  • Brain / metabolism
  • Caffeine / pharmacology*
  • Choline O-Acetyltransferase / biosynthesis
  • Choline O-Acetyltransferase / genetics
  • Cocaine / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • Enkephalins / biosynthesis
  • Enkephalins / genetics
  • Gene Expression Regulation / drug effects*
  • Genes, fos / drug effects*
  • Male
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Neurokinin B / biosynthesis
  • Neurokinin B / genetics
  • Neurons / drug effects
  • Neurons / metabolism
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P1 / biosynthesis
  • Receptors, Purinergic P1 / genetics
  • Somatostatin / biosynthesis
  • Somatostatin / genetics
  • Substance P / biosynthesis
  • Substance P / genetics


  • Biomarkers
  • Enkephalins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Purinergic P1
  • Substance P
  • Caffeine
  • Somatostatin
  • Neurokinin B
  • Amphetamine
  • Choline O-Acetyltransferase
  • Cocaine
  • Dopamine