Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jan 1997
Effects of tetrabenazine on methamphetamine-induced hyperactivity in mice are dependent on order and time-course of administration.
The ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg s.c.) in mice persisted for about 3 h. Tetrabenazine (TBZ: 4 mg/kg s.c.), a depleter of monoamines from the cytoplasmic pool did not increase ambulation on its own. Pretreatment with TBZ at 1.5 h before administration of MAP inhibited the stimulant effect of MAP. ⋯ Further, the fact that neither TBZ administration following GBR-12909 pretreatment, nor oxypertine treatment following MAP pretreatment, elicited transient hyperactivity suggests that dopamine is involved in hyperactivity elicited by post-MAP treatment with TBZ. It is also suggested that inhibition of monoamine oxidase (MAO) by MAP and dopamine displacement by TBZ may be responsible for the transient stimulation produced by 3-6 h post-MAP treatment with TBZ. It is hypothesized that the MAO inhibitory action of MAP persists after cessation of its acute stimulant effect, possibly up to 6 h after administration.
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Pharmacol. Biochem. Behav. · Jan 1997
Nitric oxide synthase inhibition impairs delayed recall in mature monkeys.
The gaseous neuromodulator nitric oxide (NO) is formed in brain regions known to mediate learning and memory processes. In rodent models, pharmacologic inhibition of NO synthesis impairs such processes. In the present study, N omega-nitro-L-arginine methyl ester (L-Name), an inhibitor of the constitutive form of the NO synthetic enzyme, was administered to seven non-aged, mature monkeys (Macaca Fascicularis, Macaca Mulatta, and Macaca Nemestrima) trained to perform a delayed matching-to-sample task (DMTS). ⋯ The detrimental effects of the 25 mg/kg dose of L-Name on DMTS accuracy were completely blocked by concurrent administration of a mole-equivalent dose of the NO amino acid precursor L-arginine. As a whole, these data suggest that L-Name impairs processes involved in delayed recall in monkeys and that this impairment is associated with attenuated synthesis of NO. However, at higher doses (> or = 25 mg/kg) this impairment is associated with aversive effects of L-Name, possibly at both central and peripheral sites.