title: Postnatal manganese exposure does not alter dopamine autoreceptor sensitivity in adult and adolescent male rats.
abstract: Administering manganese chloride (Mn) to rats on postnatal day (PD) 1-21 causes long-term reductions in dopamine transporter levels in the dorsal striatum, as well as a persistent increase in D1 and D2 receptor concentrations. Whether dopamine autoreceptors change in number or sensitivity is uncertain, although D2S receptors, which may be presynaptic in origin, are elevated in Mn-exposed rats. The purpose of this study was to determine if early Mn exposure causes long-term changes in dopamine autoreceptor sensitivity that persist into adolescence and adulthood. To this end, male rats were exposed to Mn on PD 1-21 and autoreceptor functioning was tested 7 or 70 days later by measuring (a) dopamine synthesis (i.e., DOPA accumulation) in the dorsal striatum after quinpirole or haloperidol treatment and (b) behavioral responsiveness after low-dose apomorphine treatment. Results showed that low doses (i.e., "autoreceptor" doses) of apomorphine (0.06 and 0.12 mg/kg) decreased the locomotor activity of adolescent and adult rats, while higher doses increased locomotion. The dopamine synthesis experiment also produced classic autoreceptor effects, because quinpirole decreased dorsal striatal DOPA accumulation; whereas, haloperidol increased DOPA levels in control rats, but not in rats given the nerve impulse inhibitor γ-butyrolactone. Importantly, early Mn exposure did not alter autoreceptor sensitivity when assessed in early adolescence or adulthood. The lack of Mn-induced effects was evident in both the dopamine synthesis and behavioral experiments. When considered together with past studies, it is clear that early Mn exposure alters the functioning of various dopaminergic presynaptic mechanisms, while dopamine autoreceptors remain unimpaired.
authors: Department of Psychology, 5500 University Parkway, California State University, San Bernardino, CA 92407, USA. smcdouga@csusb.edu
authors: Sanders A
authors: SA
authors: McDougall
authors: Alena
authors: A
authors: Mohd-Yusof
authors: Graham J
authors: GJ
authors: Kaplan
authors: Zuhair I
authors: ZI
authors: Abdulla
authors: Ryan J
authors: RJ
authors: Lee
authors: Cynthia A
authors: CA
authors: Crawford
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D017660:Autoreceptors / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*
chemical_list: D017660:Autoreceptors; D011954:Receptors, Dopamine; D019257:Quinpirole; D008345:Manganese; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine