Striatal c-fos induction by drugs and stress in neonatally dopamine-depleted rats given nigral transplants: importance of NMDA activation and relevance to sensitization phenomena.
Induction of the proto-oncogene c-fos occurred in cells of the striatum in response to stimuli that are known to release dopamine (DA). As revealed by fos immunocytochemistry, amphetamine (AMPH) produced c-fos induction in many cells of the medial two-thirds of the striatum of normal rats, with patchy labeling in the lateral third. The lateral patches were found to be coincident with patches of striatal neurons lacking calbindin immunoreactivity. In animals DA-depleted at birth, few fos-immunoreactive neurons were present in response to AMPH. In those with unilateral transplants of DA-rich mesencephalic tissue, c-fos induction was greater on the transplanted side. The DA D1 antagonist SCH 23390 completely blocked c-fos induction in all animals. The N-methyl-D-aspartate antagonist MK-801 also blocked c-fos induction by AMPH within the medial striatum, but intensified c-fos induction laterally in those animals with DA innervation. A second set of experiments examined the functional importance of c-fos induction in the AMPH sensitization of turning behavior that occurs in these animals. Both AMPH and stress produced turning, but only AMPH produced widespread c-fos induction, and stress-induced turning only occurred after exposure to AMPH. Treatment with MK-801 prior to AMPH administration blocked the subsequent development of stress-induced turning. Whereas a high dose of MK-801 (1.0 mg/kg) completely blocked c-fos induction, a lower dose (0.1 mg/kg) blocked c-fos induction in controls, but left patches of fos-immunoreactive neurons in lesioned animals given transplants. Thus the sensitization of transplant-related behaviors is NMDA dependent and associated with c-fos induction in host striatal neurons.
Snyder-Keller
A M
AM
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000172:deficiency*; D018492:Dopamine Antagonists; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D016202:N-Methylaspartate / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1; D013239:Stereotyped Behavior / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism* / Q000523:psychology; D013378:Substantia Nigra / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D018492:Dopamine Antagonists; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D014157:Transcription Factors; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D000661:Amphetamine; D004298:Dopamine