Unilateral dopamine depletion paradoxically enhances amphetamine-induced Fos expression in basal ganglia output structures

• Published in: Brain research Vol. 824; no. 1; pp. 81 - 88
• Main Authors: Wirtshafter, David, Asin, Karen E
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 03.04.1999; Amsterdam Elsevier; New York, NY
• Subjects: 6-Hydroxydopamine; Afferent Pathways - metabolism; Amphetamine - pharmacology; Animals; Basal Ganglia - metabolism; Biochemistry and metabolism; Biological and medical sciences; c- fos; Central nervous system; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Dopamine; Dopamine - deficiency; Dopamine Agents - pharmacology; Entopeduncular nucleus; Fundamental and applied biological sciences. Psychology; Globus pallidus; Immediate early gene; Immunohistochemistry; Male; Oxidopamine - pharmacology; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Striatum; Substantia nigra; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - pathology; Subthalamic nucleus; Vertebrates: nervous system and sense organs; Striatum; Dopamine; Substantia nigra; 6-Hydroxydopamine; Globus pallidus; Subthalamic nucleus; c- fos; Immediate early gene; Entopeduncular nucleus; Rat; Rodentia; Central nervous system; Basal ganglion; Catecholamine; Gene expression; Pallidum; Vertebrata; Mammalia; Depletion; Locus niger; Entopedoncular nucleus; Neurotransmitter; Amfetamine; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(99)01091-4

The ability of amphetamine to induce expression of the immediate early gene protein, Fos, was examined by immunocytochemistry in animals with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle. Amphetamine induced Fos expression in the globus pallidus (GP) on the intact side of the brain, but this response was greatly attenuated on the dopamine-depleted side. In contrast, amphetamine induced little Fos expression in the entopeduncular nucleus (EPN) and the substantia nigra pars reticulata (SNpr) on the intact side of the brain, but resulted in pronounced expression in these structures on the lesioned side. These findings demonstrate that unilateral dopamine depletion results in a pathophysiological state in which some responses to amphetamine are attenuated while others are paradoxically potentiated. One explanation of these effects is that amphetamine may indirectly activate excitatory inputs to the SNpr and the EPN on both sides of the brain. On the intact side, these effects would be opposed by the simultaneous activation of inhibitory pathways arising in the striatum and the GP, with the result that little Fos expression would be seen. On the dopamine-depleted side, however, engagement of these inhibitory pathways would be attenuated and the unopposed effects of the excitatory inputs mobilized by amphetamine would result in exaggerated Fos synthesis.