Pj. Bushnell et Ed. Levin, EFFECTS OF DOPAMINERGIC DRUGS ON WORKING AND REFERENCE MEMORY IN RATS, Pharmacology, biochemistry and behavior, 45(4), 1993, pp. 765-776
Changes in dopaminergic function have been associated with alterations
in motor and cognitive function in man and in animals. This study was
designed to assess the effects of dopaminergic drugs on these aspects
of conditioned behavior in animals. Male Long-Evans rats were trained
to perform an appetitive operant task that allowed daily quantificati
on of working memory (accuracy of spatial delayed nonmatching-to-posit
ion), reference memory (accuracy of visual discrimination) and motor f
unction choice lever-press latency and nosepoke interresponse time (I
RT) during delay!. The indirect dopamine agonist d-amphetamine (0.3-1.
0 mg/kg) reduced nonmatching accuracy without significantly affecting
discrimination accuracy, response latency, or nosepoke IRT. The D2/D3
agonist quinpirole (0.01-0.056 mg/kg) also decreased nonmatching accur
acy without changing discrimination accuracy, but increased choice res
ponse latency and nosepoke IRT as well. The D1 agonist SKF 38393 (1.0-
3.0 mg/kg) and the D1 antagonist SCH 23390 (0.01-0.03 mg/kg) only affe
cted nosepoke IRT, at doses below those causing response failure. The
D2 antagonist raclopride (0.056-0.177 mg/kg) exerted no significant ef
fects at doses that did not suppress responding completely. The select
ive reduction of nonmatching accuracy by d-amphetamine and quinpirole
indicates a mnemonic impairment specific to working memory (relative t
o reference memory). These results suggest further 1) that stimulation
of D2/D3, but not D1, receptors may account for the d-amphetamine-ind
uced deficit in working memory; 2) that stimulation of D2/D3 receptors
alone by quinpirole may also impair spatial working memory, but only
in conjunction with motor slowing; and 3) that antagonism of either re
ceptor type (by SCH 23390 or raclopride) does not significantly affect
memory at doses causing motor slowing and response failure.