The development of cocaine-induced behavioral sensitization is affected by discrete quinolinic acid lesions of the prelimbic medial prefrontal cortex.
The brain circuitry thought to be involved in the development of behavioral sensitization to psychostimulants consists of the mesocorticolimbic dopaminergic system and its afferent and efferent structures, including the medial prefrontal cortex (mPFC). The mPFC can be further subdivided into several regions, one of which being the prelimbic area (PL). This study sought to examine the role that the PL mPFC plays in the development of cocaine-induced behavioral sensitization. Intact and lesioned animals were treated with cocaine (10 mg/kg) or saline once daily for 14 days and tested in an open field and in a 'sniffing box' on day 1, and then again on day 16, 48 h after the last drug injection. Behavioral parameters analyzed included locomotion, rearing, sniffing and grooming. It was found that the lesion affected the development of sensitization to cocaine. In the open field, lesioned animals showed a smaller increase in locomotion and rearing, but a larger increase in grooming as compared to the intact animals. While total sniffing scores in the sniffing box remained unchanged with repeated cocaine in the non-lesioned group, the lesioned group showed a decrease in sniffing. Finally, similar to what was seen in the open field, lesioned rats showed a strong tendency towards increased grooming. These results show that small discrete lesions of the PL mPFC can affect the development of behavioral sensitization to cocaine in a characteristic way. It is suggested that this effect might be mediated by the destruction of descending glutamatergic projections from the mPFC to the ventral tegmental area and/or nucleus accumbens.
Tzschentke
T M
TM
Dept. Neuropharmacology, Zoological Institute, University of Tübingen, Mohlstrasse 54/1, 72074 Tübingen, Germany. thomas.tzschentke@uni-tuebingen.de
Schmidt
W J
WJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced; D009412:Nerve Fibers / Q000502:physiology; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D017378:Quinolinic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D012903:Smell / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D017378:Quinolinic Acid; D003042:Cocaine