Journal of Neuroscience, Vol 6, 2684-2690, Copyright © 1986 by Society for Neuroscience
Retardation of associative learning in the rabbit by an adenosine analog as measured by classical conditioning of the nictitating membrane response
L Winsky and JA Harvey
A series of 5 experiments examined the effects of the adenosine agonist,
N6-(L-phenylisopropyl) adenosine (L-PIA) and its isomer, D- PIA, on the
acquisition of conditioned responses in the rabbit. Extension of the
nictitating membrane was classically conditioned to a tone and light
stimulus presented for 800 msec before delivery of a 100 msec shock--the
unconditioned stimulus--to the skin over the paraorbital region of the
head. L-PIA (5.0 mumol/kg) retarded the rate of acquisition of conditioned
responses to both the tone- and light- conditioned stimuli, while D-PIA, at
doses of 5.0 and 10.0 mumol/kg, had no significant effect. Control
experiments employing the explicitly unpaired presentations of tone, light,
and shock stimuli indicated that the retarded acquisition of conditioned
responses produced by L-PIA was due to an action on associative learning.
L-PIA had no effect on the threshold of the shock's eliciting of the
unconditioned response nor on the amplitude of the elicited response, but
produced a large and significant reduction in the ability of the
tone-conditioned stimulus to evoke conditioned responses. It was concluded
that L-PIA blocked the rate of associative learning by decreasing the
excitatory properties of conditioned stimuli. These effects of L-PIA
suggest that endogenous adenosine may act to modulate the rate of
associative learning.