The constitutively expressed (CC)
Homer protein Homer2a/b actively regulates behavioral and neurochemical sensitivity to
cocaine in both rats and mice. The present study employed standard immunoblotting techniques to compare the effects of withdrawal from repeated
cocaine (7 x 30 mg/kg) upon the
protein expression of Homer2a/b with a related CC-
Homer protein Homer1b/c, as well as their associated
glutamate receptors, within brain regions implicated in
cocaine addiction. To determine whether or not the observed
cocaine-induced changes in Homer and
glutamate receptor expression generalized across mammalian species, immunoblotting was conducted on tissue derived from both male Sprague-Dawley rats and male C57BL/6J mice. In both species, withdrawal from repeated
cocaine administration down-regulated Homer1b/c and Homer2a/b within the shell, but not the core, of the nucleus accumbens (NAC), and the reduced Homer levels were accompanied by decreases in
mGluR1a, NR2a and NR2b. In the PFC, repeated
cocaine up-regulated Homer2a/b,
mGluR1 and NR2b expression, without affecting Homer1b/c levels.
Cocaine-induced increases in Homer1b/c, Homer2a/b,
mGluR1a and NR2a were observed in the hippocampus of both rats and mice, while in dorsal striatum, NR2a levels were elevated but Homer and Group1 mGluR levels were unchanged. Thus, withdrawal from repeated
cocaine alters the expression of CC-Homer
isoforms and their associated
glutamate receptors in a regionally-distinct manner. As CC-
Homer proteins, Group1 mGluRs and
NMDA receptors actively regulate
cocaine-induced neuroplasticity in vivo, these data support the hypothesis that
cocaine-induced changes in mGluR-Homer-
NMDA signaling pathways may be important neuroadaptations mediating the enduring changes in behavior produced by repeated
cocaine experience.