The effects of acute or repeated cocaine administration on nerve terminal glutamate within the rat mesolimbic system

doi:10.1016/S0306-4522(01)00274-3

Neuroscience

Volume 106, Issue 1, 3 September 2001, Pages 15-25

https://doi.org/10.1016/S0306-4522(01)00274-3 Get rights and content

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.

Section snippets

Animal housing

Male, Sprague–Dawley rats (initial weight 200–225 g; Harlan, Indianapolis, IN, USA) were doubly housed at the Portland Veteran’s Administration Medical Center Veterinary Medical Unit, in a temperature- and light-controlled environment with a 12-h day/night cycle. The animals had free access to food and water and were drug-naive at the start of the experiment. They were allowed to acclimate to their cages for at least 5 days. Rats were handled daily to provide habituation to the testing

Locomotor activity

Baseline locomotor activity did not differ between any of the groups (data not shown). Locomotor activity was monitored on the first day of repeated cocaine administration, and on the challenge day. The acute cocaine and repeated cocaine groups received cocaine on the challenge day. The first day of cocaine administration (sensitized and non-sensitized groups) resulted in a significant increase in locomotor activity (Table 1) compared to the groups that received saline (saline and acute

Discussion

In the current study acute cocaine administration resulted in a significant decrease in nerve terminal glutamate immunolabeling in the NAc core and shell. The expression of behavioral sensitization was not associated with significant changes in glutamate immunoreactivity in the NAc, although glutamate immunolabeling tended to be lower in the cocaine-sensitized compared to the saline group. However, there does appear to be a positive relationship between horizontal activity following a cocaine

Conclusions

We report that a significant loss in nerve terminal glutamate immunolabeling in the NAc core, and shell 3 days after an acute dose of cocaine, is attenuated following sensitization to repeated cocaine. In cocaine-sensitized animals, greater horizontal activity following a cocaine challenge was positively associated with increased glutamate immunolabeling in the NAc core, but not the shell. This suggests, at least in the NAc core, that the attenuation of nerve terminal glutamate immunolabeling

Acknowledgements

The authors are grateful for the assistance of the Dr. Tamara Phillips laboratory in assessing locomotor activity. The authors are also grateful to Cynthia Moore for her expert assistance. This work was supported by a postdoctoral fellowship from the Pharmaceutical Research and Manufacturers of America Foundation (L.B.K.), the Department of Veterans Affairs Merit Review Program and the Smokeless Tobacco Research Council (C.K.M.).

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The effects of acute or repeated cocaine administration on nerve terminal glutamate within the rat mesolimbic system

Abstract

Section snippets

Animal housing

Locomotor activity

Discussion

Conclusions

Acknowledgements

Neuroscience

Brain Res. Brain Res. Rev.

Drug Alcohol Depend.

Brain Res. Brain Res. Rev.

Prog. Neurobiol.

Neuroscience

Brain Res.

Brain Res. Brain Res. Rev.

Neuroscience

Neurosci. Lett.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Brain Res. Rev.

Brain Res.

Brain Res.

Neuropharmacology

Prog. Neurobiol.

Neuroscience

Brain Res.

Neuroscience

Context-specific cross-sensitization between systemic cocaine and intra-accumbens AMPA infusion in the rat

Psychopharmacology

Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat

J. Comp. Neurol.

The patterns of afferent innervation of the core and shell of the ‘accumbens’ part of the rat ventral striatum: Immunohistochemical detection of retrogradely transported fluoro-gold

J. Comp. Neurol.

Methamphetamine alters presynaptic glutamate immunoreactivity in the caudate nucleus and motor cortex

Synapse

Repeated cocaine alters glutamate receptor subunit levels in the nucleus accumbens and ventral tegmental area of rats that develop behavioral sensitization

J. Neurochem.

Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: Common adaptations among cross-sensitizing agents

J. Neurosci.

Neuroadaptations in ionotropic and metabotropic glutamate receptor mRNA produced by cocaine treatment

J. Neurochem.