Cocaine and Pavlovian fear conditioning: dose-effect analysis.
Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1-15mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15mg/kg) displayed significantly less contextual and cued memory, compared to saline control animals. Conversely, mice pre-treated with a very low dose of cocaine (0.1mg/kg) showed significantly enhanced fear memory for both context and tone, compared to controls. These results were not due to cocaine's anesthetic effects, as shock reactivity was unaffected by cocaine. The data suggest that despite cocaine's reputation as a performance-enhancing and anxiogenic drug, this effect is seen only at very low doses, whereas a moderate dose disrupts hippocampus and amygdala-dependent fear conditioning.
Wood
Suzanne C
SC
Department of Psychology, University of California, San Diego, 9500 Gilman Drive 0109, LaJolla, CA 92093-0109, United States. scwood@ucsd.edu
Fay
Jonathan
J
Sage
Jennifer R
JR
Anagnostaras
Stephan G
SG
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D005239:Fear; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D051379:Mice
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine