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Downregulation of κ‐opioid receptors in basolateral amygdala and septum of rats withdrawn for 14 days from an escalating dose “binge” cocaine administration paradigm

There is evidence showing that the opioid systems play an important role in cocaine addiction; fewer studies have examined their roles in cocaine withdrawal. This study was conducted to determine whether cocaine or chronic withdrawal from cocaine alters the receptor component of the κ‐opioid system. Male Fischer rats were injected with saline or cocaine (3 × 15 mg/kg/day for 4 days, 3 × 20 mg/kg/day for 4 days, 3 × 25 mg/kg/day for 4 days, and 3 × 30 mg/kg/day for 2 days), three times daily at 1‐h intervals in an escalating dose paradigm for 14 days. Identically treated rats were withdrawn from cocaine or saline for 14 days. We performed quantitative autoradiographic mapping of κ‐opioid receptors (KOP‐r) in the brains of rats treated with this escalating dose “binge” cocaine administration paradigm and of rats withdrawn from cocaine for 14 days. A significant condition (chronic/withdrawal) effect was shown across all regions analyzed. A significant increase in [3H]CI‐977 binding to KOP‐r was detected in the septum of rats treated with an escalating dose binge cocaine administration paradigm and killed 30 min after the last cocaine injection. In contrast, there was a decrease in KOP‐r binding in the septum and the basolateral amygdala of rats withdrawn for 14 days from chronic escalating dose binge cocaine administration, compared to rats at the end of 14 days chronic escalating dose cocaine administration. These results reconfirm and extend that KOP‐r undergoes upregulation in response to chronic binge cocaine administration here, with an escalating dose. The observed lowering in KOP‐r binding, which was shown in two brain regions of cocaine withdrawn animals, might contribute to the persistent dysphoria reported a long time after the discontinuation of the drug. Synapse 61:820–826, 2007. © 2007 Wiley‐Liss, Inc.