Dopaminergic function in the neostriatum and nucleus accumbens of young and aged Fischer 344 rats.
Age-dependent alterations in behavioral and neuronal functioning were assessed in young (2-3 month), middle-aged (12 month), and aged (24 month) Fischer 344 rats treated with the indirect dopamine agonist amphetamine (2.25 or 5 mg/kg), the D1 agonist SKF 38393 (7.5, 15, 30 mg/kg), or the D2 agonist quinpirole (0.3, 1.0, 3.0 mg/kg). Drug-induced changes in activity and stereotypy were measured during a 90-min testing session, with Fos immunohistochemistry being used to assess the neuronal response to dopamine agonist treatment. As expected, aged rats given amphetamine (5 mg/kg) had fewer activity counts and higher stereotypy scores than young rats. Middle-aged rats also had fewer activity counts but were similar in stereotypy scores to young rats. Amphetamine also induced different patterns of Fos immunoreactivity in the neostriatum and nucleus accumbens of young and aged rats, as Fos expression in aged rats exhibited a distinctive dorsal to ventral pattern of decline. In general, SKF 38393 had few age-related actions, although aged rats did show a slight relative increase in stereotypy. In contrast, the D2 agonist quinpirole substantially enhanced the motor activity and Fos expression of young rats, while only modestly affecting aged rats. Hence, these results suggest that the D2 receptor is more vulnerable to the effects of aging than the D1 receptor.
Crawford
C A
CA
Mental Retardation Research Center, University of California School of Medicine, Los Angeles 90024, USA.
Levine
M S
MS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine; D004298:Dopamine