title: The effects of acute or repeated cocaine administration on nerve terminal glutamate within the rat mesolimbic system.
abstract: Cocaine administration alters glutamate function within several brain regions. Using quantitative electron microscopic immunocytochemistry, the present study investigated the effect of repeated intermittent cocaine (resulting in behavioral sensitization) or acute cocaine administration on the density of glutamate immunogold labeling within nerve terminals. Rats were treated daily with saline or cocaine for 7 days. Following a 14-day withdrawal animals were challenged with saline or cocaine. On the challenge day, most (75%) animals that received cocaine repeatedly showed a heightened locomotor response to cocaine compared to the first day of cocaine administration, and were considered behaviorally sensitized.Three days after the challenge, glutamate immunogold labeling was quantified in nerve terminals making asymmetrical synaptic contacts within the core and shell of the nucleus accumbens, ventral tegmental area and medial prefrontal cortex. There was a decrease in such labeling in the nucleus accumbens in the group receiving acute cocaine. Locomotor activity was positively correlated with glutamate immunolabeling within nerve terminals in the nucleus accumbens core only for the cocaine-sensitized group. Nerve terminal glutamate immunolabeling in the nucleus accumbens core, but not the shell, was increased in the non-sensitized compared to the cocaine-sensitized group. In the ventral tegmental area, glutamate immunolabeling was significantly higher in the cocaine-sensitized compared to the acute cocaine group. In the prefrontal cortex, there were no significant differences in glutamate immunogold labeling between treatment groups. This study indicates that acute cocaine administration significantly decreases nerve terminal glutamate immunoreactivity in the nucleus accumbens. We suggest that sensitization results in differential changes in the nucleus accumbens core versus the shell, and may alter presynaptic mechanisms regulating glutamate release or re-uptake in the core.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland, OR 97201, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Kozell
authors.forename: C K
authors.initials: CK
authors.lastname: Meshul
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004334:Drug Administration Schedule; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003042:Cocaine