Cancer chemotherapy impairs contextual but not cue-specific fear memory.
This study examined the effects of a standard breast cancer chemotherapeutic protocol on learning and memory in rats. Ovariectomized rats were treated once a week for 3 weeks with a combination of cyclophosphamide and doxorubicin prior to training in a classical fear conditioning task. Training took place 1 week after the final treatment. During the training session, an auditory stimulus (a tone) was paired with a mild foot-shock. The resulting conditioned fear to the tone (cue-specific fear) and to the training environment (contextual fear) was measured in subsequent test sessions. Chemotherapy did not affect the acquisition of the conditioned response (freezing) during the training session or the expression of fear during the tone test session. In contrast, rats treated with cyclophosphamide and doxorubicin exhibited decreased freezing during the context test session, suggestive of a specific deficit in hippocampal-related learning and memory. Together, these data indicate that administration of cyclophosphamide and doxorubicin may have toxic effects on the hippocampus and results in specific learning deficits shortly after treatment has ended.
Macleod
Jill E
JE
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH 03755, United States.
DeLeo
Joyce A
JA
Hickey
William F
WF
Ahles
Tim A
TA
Saykin
Andrew J
AJ
Bucci
David J
DJ
D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000187:drug effects*; D003463:Cues; D003520:Cyclophosphamide / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D005239:Fear; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced*; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D004317:Doxorubicin; D003520:Cyclophosphamide