Nerve terminal glutamate immunoreactivity in the rat nucleus accumbens and ventral tegmental area after a short withdrawal from cocaine.
Cocaine administration has been shown to alter glutamate transmission in numerous studies. Using quantitative electron microscopic immunogold labeling, our laboratory has previously reported that nerve terminal glutamate immunoreactivity is transiently altered following cocaine administration. The present study was undertaken to examine presynaptic nerve terminal glutamate immunoreactivity at shorter time points after withdrawal from cocaine. Animals received saline or cocaine for 7 days followed 3 days later by a cocaine or saline challenge. Most (>75%) cocaine-challenged animals had a heightened locomotor response to cocaine compared to the first day of cocaine and were considered behaviorally sensitized. One day after the challenge, glutamate immunogold-labeling was quantified in nerve terminals making asymmetrical synaptic contacts within the core and shell of the nucleus accumbens and ventral tegmental area. A single dose of cocaine did not alter the density of presynaptic nerve terminal glutamate immunoreactivity in the nucleus accumbens (NAc) or ventral tegmental area (VTA). The density of nerve terminal glutamate immunoreactivity in the shell, but not the core, was significantly increased in the animals receiving repeated cocaine. In the VTA the density of nerve terminal glutamate immunoreactivity did not change in the cocaine-sensitized group, but was significantly increased in the nonsensitized group. The finding that repeated cocaine treatment increased glutamate nerve terminal immunolabeling within the nucleus accumbens shell, but not the core, supports the hypothesis that glutamate synapses in the core and shell are differentially sensitive to repeated cocaine administration. Overall, our study does not support a role for changes in presynaptic glutamate in the development of behavioral sensitization.
Kozell
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LB
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
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D000818:Animals; D003042:Cocaine; D018698:Glutamic Acid / Q000032:analysis*; D007120:Immunochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure
D018698:Glutamic Acid; D003042:Cocaine