Repeated treatment with ascorbate or haloperidol, but not clozapine, elevates extracellular ascorbate in the neostriatum of freely moving rats

Abstract

Acute administration of neuroleptic drugs alters the extracellular level of ascorbate in the neostriatum, and increasing evidence suggests a role for this vitamin in the behavioral, and possibly therapeutic, effects of these drugs. To shed further light on this issue, extracellular ascorbate was recorded in the neostriatum and nucleus accumbens of awake, behaving rats following chronic treatment with either classical (haloperidol) or atypical (clozapine) neuroleptics or ascorbate itself. Electrochemically modified, carbon-fiber microelectrodes were lowered in place the day after the last of 21 daily injections of either haloperidol (0.5 mg/kg, SC), clozapine (20 mg/kg, IP), sodium ascorbate (500 mg/kg, IP) or vehicle. Voltammetric measurements were obtained during quiet rest and following administration of d-amphetamine (2.5 mg/kg). Repeated treatment with either haloperidol or ascorbate elevated basal extracellular ascorbate and potentiated the amphetamine-induced increase in ascorbate release in neostriatum but not nucleus accumbens. Both treatment groups also showed a significant increase in amphetamine-induced sniffing and repetitive head movements compared to vehicle-treated animals. In contrast, repeated clozapine had no effect on extracellular ascorbate in either neostriatum or nucleus accumbens, but increased the locomotor response to an amphetamine challenge. Thus, to the extent that increases in neostriatal ascorbate exert neuroleptic-like effects, such effects are likely to parallel haloperidol rather than clozapine.

Chronic haloperidol produces a time- and dose-related slowing of lick rhythm in rats: implications for rodent models of tardive dyskinesia and neuroleptic-induced parkinsonism

“…In addition, previous reports suggest that, on a mg/kg basis, similar haloperidol doses in rats (Schotte et al 1996) and humans (Nordstroom et al 1992) (around 0.15 mg/kg in both) produce similarly high striatal receptor occupancies in both species. In regard to length of haloperidol treatment, the 15 weeks used here is within the range of treatment durations reported to produce, in rats, a considerable number of behavioral, biochemical, physiological or anatomical effects, including VCMs (e.g., Gunne and Hagstrom 1983), computer scored oral movements (Ellison and See 1989), reduction in basal levels of DA (Ichikawa and Meltzer 1991), depolarization block of substantia nigra compacta neurons (Bunney and Grace, 1978), dopamine receptor supersensitivity in the striatum (Burt et al 1977), induction of striatal perforated synapses (Meshul and Casey 1989), and elevation of striatal extracellular ascorbate (Pierce et al 1994). Thus, the duration of treatment seems appropriate.…”

Democratic Legitimation of Delegated Legislation—a Comparative View on the American, British and German Law

“…They are reluctant to declare the 'fourth branch, a haphazard deposit of irresponsible agencies and uncoordinated powers' 60 as unconstitutional. 61 The independent 55 regulatory commissions seem to be too strongly rooted in American state practice as the 'principal structural development' of the 20th century 62 and as 'part of legal folklore' 63 . Suggesting the German model of confining the empowerment to delegates which are directly accountable to elected representatives of the people does not seem to be very promising.…”