Prenatal exposure to cocaine impairs neuronal coding of attention and discriminative learning.
Cingulate cortex and related areas of the thalamus are critically involved in the mediation of discriminative avoidance learning, wherein rabbits step in response to an acoustic conditional stimulus (CS+) to avoid foot shock and they learn to ignore a different acoustic stimulus (CS-) not followed by shock. Studies of multi-unit neuronal activity recorded simultaneously in many cingulothalamic areas have documented massive learning-related neuronal firing changes during the course of behavioral acquisition. Stimulated by findings (this volume) of neurobiological changes in anterior cingulate cortex in rabbits exposed in utero to cocaine, we investigated behavioral learning and correlated neuronal activity in several cingulothalamic areas in cocaine-exposed rabbits. In an initial study, training-induced enhancement of cingulate cortical neuronal firing in response to the CS+ and CS- was abolished in rabbits exposed to cocaine in utero. Yet discriminative neuronal activity (greater firing in response to the CS+ than to the CS-) did develop during training, and behavioral learning was normal in the cocaine-exposed rabbits. In a second study, we reduced the salience of the CS+ and CS- by employing 200 msec CSs rather than standard 500 msec CSs. Early training-stage development of anterior cingulate cortical discriminative neuronal activity was abolished, the elicited neuronal discharge profiles were altered, and behavioral learning was impaired in rabbits exposed to cocaine, relative to saline-exposed controls. The specificity of these changes to low-salience CSs suggested that prenatal cocaine results in disturbed associative attentional processes of anterior cingulate cortex in adult rabbits. Consideration of the neuronal response profile alterations together with other reported neurobiological changes suggested that the cocaine-related attentional deficit is due to impaired dopaminergic afferent activation of GABA neurons in anterior cingulate cortex.
Department of Psychology, Beckman Institute for Advanced Science and Technology, Urbana, Illinois 61801, USA.
M
M
Gabriel
C
C
Taylor
D000161:Acoustic Stimulation; D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000633:toxicity*; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004597:Electroshock; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D008960:Models, Psychological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D013045:Species Specificity; D013787:Thalamic Nuclei / Q000187:drug effects* / Q000502:physiology
D003042:Cocaine