Background: We recently established a new animal model of cue-induced methamphetamine seeking after prolonged voluntary abstinence (Caprioli et al. Biol Psychiatry 2015). Here, we studied the role of central amygdala (CeA) in this form of relapse. Methods: We trained rats to self-administer palatable food (6 sessions, 2-h/day) and then methamphetamine (15 sessions, 2-h/day). Next, voluntary abstinence (14 sessions) was achieved via a discrete choice procedure between methamphetamine and palatable food (20 trials/day). We then assessed cue-induced methamphetamine seeking in extinction tests. We first determined the effect of systemic injections of the dopamine D1-receptor antagonist SCH39166 on cue-induced methamphetamine seeking and Fos expression in central amygdala (CeA) and areas that project to CeA: basolateral amygdala (BLA), anterior insular cortex (AIC), paraventricular thalamus (PVT), and ventral subiculum (vSub). Next, we determined the effect of CeA and BLA injections of SCH39166 on cue-induced methamphetmaine seeking. Finally, we combined the retrograde tracer cholera toxin subunit-B (CTb, injected into CeA) with Fos to determine neuronal activation in the projection areas. Results: Cue-induced methamphetamine seeking after voluntary abstinence increased Fos expression in CeA, AIC, and PVT, but not in BLA and vSub; both Fos expression and drug seeking were decreased by systemic SCH39166 injections. CeA, but not BLA, SCH39166 injections decreased cue-induced methamphetamine seeking. Double-labeling analysis of CTb+Fos showed that cue-induced methamphetamine-seeking was associated with selective activation of AIC neurons that project to CeA. Conclusions: Results demonstrate a critical role of CeA in cue-induced relapse of methamphetamine seeking after voluntary abstinence and suggest a role of AIC projections to CeA in this relapse. This work was supported by NIDA/NIH.
Role of central nucleus of amygdala in cue-induced relapse to methamphetamine seeking after voluntary abstinence
C. Cifani;
2015-01-01
Abstract
Background: We recently established a new animal model of cue-induced methamphetamine seeking after prolonged voluntary abstinence (Caprioli et al. Biol Psychiatry 2015). Here, we studied the role of central amygdala (CeA) in this form of relapse. Methods: We trained rats to self-administer palatable food (6 sessions, 2-h/day) and then methamphetamine (15 sessions, 2-h/day). Next, voluntary abstinence (14 sessions) was achieved via a discrete choice procedure between methamphetamine and palatable food (20 trials/day). We then assessed cue-induced methamphetamine seeking in extinction tests. We first determined the effect of systemic injections of the dopamine D1-receptor antagonist SCH39166 on cue-induced methamphetamine seeking and Fos expression in central amygdala (CeA) and areas that project to CeA: basolateral amygdala (BLA), anterior insular cortex (AIC), paraventricular thalamus (PVT), and ventral subiculum (vSub). Next, we determined the effect of CeA and BLA injections of SCH39166 on cue-induced methamphetmaine seeking. Finally, we combined the retrograde tracer cholera toxin subunit-B (CTb, injected into CeA) with Fos to determine neuronal activation in the projection areas. Results: Cue-induced methamphetamine seeking after voluntary abstinence increased Fos expression in CeA, AIC, and PVT, but not in BLA and vSub; both Fos expression and drug seeking were decreased by systemic SCH39166 injections. CeA, but not BLA, SCH39166 injections decreased cue-induced methamphetamine seeking. Double-labeling analysis of CTb+Fos showed that cue-induced methamphetamine-seeking was associated with selective activation of AIC neurons that project to CeA. Conclusions: Results demonstrate a critical role of CeA in cue-induced relapse of methamphetamine seeking after voluntary abstinence and suggest a role of AIC projections to CeA in this relapse. This work was supported by NIDA/NIH.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.