Effects of Psychoactive Drugs on Short-Term Memory in Rats and Rhesus Monkeys

Abstract

ABSTRACT-To examine the effects of drugs on short-term memory in animals, the delayed discri mination experiment in rats and the delayed matching to sample experiment in rhesus monkeys were conducted. Nicotine at 0.125 mg/kg, s.c. in rats and at 0.5 mg/kg, s.c. in monkeys increased the per centages of correct choices. Scopolamine at 0.06-0.12 mg/kg, s.c. in rats and at 0.015 mg/kg, s.c. in monkeys decreased the percentages of correct choices. However, supposedly memory-specific, delay time-dependent disruptive effects by scopolamine were found only in monkeys. Diazepam at 0.5-2 mg/kg, s.c. did not change the correct choices in rats. However, diazepam at 1-4 mg/kg, i.g. de creased the correct choices in monkeys regardless of the delay time. Chlorpromazine at 0.25-1.5 mg/kg, s.c. showed inconsistent effects in rats. In monkeys, chlorpromazine at 0.25-0.5 mg/kg, s.c. had no effect. These results suggested that using both rats and monkeys would be useful for evaluating the effects of drugs on memory.

Effects of nicotine and mecamylamine on cognition in rhesus monkeys

“…This confirms and extends previous observations of improved DMS performance in either young adult or aged monkeys following nicotine administration (Buccafusco and Jackson 1991;Buccafusco et al 1999;Elrod et al 1988;Hironaka et al 1992). Although perhaps unsurprising given the wide distribution of nAChRs in the primate brain (see (Court et al 2000a) for review) the present results clearly demonstrate that the memory enhancing effects of nicotine extend beyond visual recognition memory for stimulus hue in the macaque.…”

Differential effects of scopolamine and lorazepam on working memory maintenance versus manipulation processes

“…Given that memory load was not manipulated (i.e., each trial involved presentation of only one pattern), presumably storage requirements were held constant and only rehearsal requirements changed as a function of delay; thus, results suggest that scopolamine impairs both the storage and rehearsal components of working memory, whereas diazepam impairs only storage. A similar pattern of results was found in a comparison of effects of diazepam and scopolamine on a delayed matching-to-sample task in rhesus monkeys (Hironaka et al, 1992): Scopolamine produced delay-dependent impairment, whereas diazepam produced delay-independent impairment.…”

“…In addition to adding to the accumulating body of evidence supporting the distinction between maintenance and manipulation processes, these results suggest that the cholinergic system may be relatively more involved in maintenance processes, whereas the GABAergic system may be relatively more involved in manipulation processes. The suggestion that the cholinergic system is relatively more involved in maintenance processes is also supported by the finding that scopolamine but not diazepam produced delay-dependent impairment in a delayed matching-to-sample task in rhesus monkeys (Hironaka et al, 1992). Results of previous cognitive psychopharmacological studies in healthy volunteers also suggest different patterns of effects on working memory maintenance and manipulation as a function of neurochemical/ pharmacological mechanism of action.…”

“…As described in detail below, the present comparison between lorazepam and scopolamine was motivated by evidence from both nonhuman animal and human studies that benzodiazepines and anticholinergics may differ in their effects on specific working memory processes. Both benzodiazepines and scopolamine have been shown to impair performance on working memory tasks (e.g., delayed matching-to-sample tasks) in both rats and nonhuman primates (Chrobak & Napier, 1992;Hironaka, Miyata, & Ando, 1992;Ingles, Beninger, Jhamandas, & Boegman, 1993;White, Simson, & Best, 1997). Additional support for the involvement of the cholinergic system, in particular, in working memory, comes from findings that the acetylcholinestrase inhibitor physostigmine enhances working memory performance in animals, healthy adult volunteers, and patients with Alzheimer's disease (Furey, Pietrini, Alexander, Schapiro, & Horwitz, 2000;Furey, Pietrini, & Haxby, 2000;Furey et al, 1997;Glasky, Melchior, Pirzadeh, Heydari, & Ritzmann, 1994;Levy et al, 1994;Sano et al, 1993;Terry, Jackson, & Buccafusco, 1993).…”

“…Although the task used in Robbins et al (1997;and in Hironaka et al, 1992) required that material be maintained over a particular duration, it did not require that any manipulations be performed on the material. Interestingly, results of a study recently conducted in our laboratory with lorazepam and scopolamine suggest that when maintenance requirements are relatively low but manipulation is required, the opposite pattern of results is observed (Mintzer & Griffiths, 2003).…”