TY - JOUR
T1 - Inhibition of CaMKII in the nucleus accumbens shell decreases enhanced amphetamine intake in sensitized rats
AU - Loweth, Jessica A.
AU - Baker, Lorinda K.
AU - Guptaa, Tarra
AU - Guillory, Anitra M.
AU - Vezina, Paul
N1 - Funding Information:
This study was supported by National Institutes of Health grants DA-09397 (P.V.), T32-DA-07255 (T.G., A.M.G.) and F31-DA-022834 (J.A.L.).
PY - 2008/10/24
Y1 - 2008/10/24
N2 - 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 (1.5 mg/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 μg/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 μl/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.
AB - 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 (1.5 mg/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 μg/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 μl/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.
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U2 - 10.1016/j.neulet.2008.08.004
DO - 10.1016/j.neulet.2008.08.004
M3 - Article
C2 - 18694805
AN - SCOPUS:51349128029
SN - 0304-3940
VL - 444
SP - 157
EP - 160
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -