Accepted for publication (PostPrint)
Microinjection of the calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 into the nucleus accumbens (NAcc) shell impairs expression of the sensitized locomotion and NAcc dopamine (DA) overflow normally observed in psychostimulant-exposed rats. Based on these results, we investigated the effect of NAcc shell KN-93 on the enhanced amphetamine (AMPH) intake normally observed in AMPH- relative to saline-exposed rats. Rats were administered five injections of either AMPH (1.5mg/kg, i.p.) or saline, one injection every 2-3 days. Fourteen days following the last injection, they were trained to self-administer AMPH (200 microg/kg/infusion, i.v.) first on fixed ratio schedules (FR) and then on a progressive ratio schedule of reinforcement (PR). As expected, AMPH-exposed rats worked harder and obtained significantly more drug infusions than saline-exposed rats on the PR schedule. After 4 days of stable responding, all rats were bilaterally microinjected with KN-93 (1 or 10 nmol/0.5 microl/side) into the NAcc shell, 2 min prior to the beginning of the self-administration session. Inhibiting CaMKII in this site reduced the enhanced drug intake observed in AMPH-exposed rats to levels no longer significantly different from those of saline-exposed rats. Responding in these latter controls was not affected by KN-93 nor did KN-93 affect responding in AMPH-exposed rats when it was infused into the NAcc core. Thus, in a manner similar to what has been reported for sensitized locomotion and NAcc DA overflow, these results suggest that inhibiting CaMKII in the NAcc shell attenuates the enhanced motivation to obtain a drug reinforcer that is normally displayed in AMPH-exposed rats.
Loweth, Jessica; Baker, Lorinda; Guptaa, Tarra; Guillory, Anitra; and Vezina, Paul, "Inhibition Of Camkii in the Nucleus Accumbens Shell Decreases Enhanced Amphetamine Intake in Sensitized Rats" (2008). School of Osteopathic Medicine Faculty Scholarship. 12.
Loweth JA, Baker LK, Guptaa T, Guillory AM, Vezina P. Inhibition of CaMKII in the nucleus accumbens shell decreases enhanced amphetamine intake in sensitized rats. Neuroscience Letters. 2008 Oct 24;444(2):157-60. Epub 2008 Aug 7. doi: 10.1016/j.neulet.2008.08.004. PMID: 18694805. PMCID: PMC2703195.