The role of the GABA(A) agonist muscimol on memory performance: reward contingencies determine the nature of the deficit.
A matching-to-position (MTP) paradigm was altered to influence the type of associations a rat would use to solve the task. Our main behavioral manipulation was the application of the differential outcomes procedure (DOP). The DOP involves correlating each to-be-remembered event with a distinct reward condition. This procedure results in the development of unique reward expectancies that enhance and guide choice behavior. Such distinct reward expectancies are not formed when either a common or random assignment of reward is used (a non-differential outcomes procedure [NOP]). Intracerebroventricular infusions of the amnestic agent muscimol (GABA(A) agonist) or aCSF were delivered to male rats trained on a delayed MTP task that implemented either the DOP or the NOP. Muscimol impaired performance in a dose dependent fashion in both groups--but the nature of the deficit differed as a function of reinforcement contingencies. Rats trained with the DOP displayed a non-mnemonic delay-independent impairment: performance at all delay intervals was disrupted. In contrast, NOP-trained rats displayed a delay-dependent impairment demonstrating that muscimol can also have memory-disrupting effects. The difference in pattern of impairment appears to be a function of the associations formed during training and the type of cognitive strategies involved in maintaining behavior on a conditional delayed discrimination task when reinforcement contingencies are varied. Thus, these results demonstrate that increasing GABA(A) receptor activation impairs a range of associative and memory functions.
Ramirez
Donna R
DR
Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, Binghamton NY 13902, USA.
Buzzetti
Robert A
RA
Savage
Lisa M
LM
D000818:Animals; D002555:Cerebrospinal Fluid; D003216:Conditioning, Operant / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012201:Reward
D018755:GABA Agonists; D009118:Muscimol