Signaling molecules involved in stress-induced reinstatement of Esc-C CPP

While the current studies identified that the NMDAR and NO-signaling play a
role in stress-induced reinstatement of Fix-C CPP, an effective test drug against Esc-C
memory was not identified. Since Esc-C memory represents a ‘stronger’ and more
‘resistant’ type of drug memory compared to Fix-C memory, there is a need to identify
the signaling pathways that contribute to stress-related re-emergence of extinguished Esc-
C CPP. It appears that the interaction between stress-related molecules and those that
mediate reinstatement are different between Fix-C and Esc-C. Because modulation of
ionotropic glutamate receptors was ineffective at attenuating stress-induced reinstatement
of Esc-C CPP, a possible alternative to target is metabotropic glutamate receptors
(mGluRs). Specifically, the mGluR2/3 agonist LY379268 has been shown to inhibit
cocaine seeking in preclinical animal models and decrease stress-induced relapse due to
its anxiolytic effects. Similarly, the mGluR1/5 antagonists, 2-methyl-6-
(phenylethynyl)pyridine and 3-[2- methyl-4-thiazolyl)ethynyl]pyridine, have shown to be
effective in preclinical models of cocaine addiction (Uys & LaLumiere, 2008). Hence, an
investigation of these mGluRs as well as other potential candidates may identify
pharmacological agents that could attenuate stress-induced reinstatement of the ‘strong’
Esc-C memory. Successful suppression of stress-induced reinstatement of Esc-C memory
should yield effective pharmacotherapies against stress-induced relapse to drug use.


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