Differences in the regional and cellular localization of c-fos messenger RNA induced by amphetamine, cocaine and caffeine in the rat.
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)
Johansson
B
B
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Lindström
K
K
Fredholm
B B
BB
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D015287:Neurokinin B / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis / Q000235:genetics; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics; D013373:Substance P / Q000096:biosynthesis / Q000235:genetics
D015415:Biomarkers; D004745:Enkephalins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D013373:Substance P; D002110:Caffeine; D013004:Somatostatin; D015287:Neurokinin B; D000661:Amphetamine; D002795:Choline O-Acetyltransferase; D003042:Cocaine; D004298:Dopamine