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1.
Figure 8

Figure 8. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

Localization of infusion sites in the medial NAc core and CPu (+1.2 through +2.2 mm from Bregma, Paxinos and Watson, 1998).

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.
2.
Figure 5

Figure 5. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

(a) Reinstatement induced by 1 μg β-endorphin is blocked by intra-NAc pretreatment with CTAP or naloxone, but not naltrindole. (b) Reinstatement induced by 3 μg thiorphan is blocked by intra-NAc pretreatment with naltrindole or naloxone, but not CTAP. Data represent the mean ± SEM for β-endorphin/antagonist (n = 9–17 animals/treatment) and thiorphan/antagonist (n = 8–14 animals/treatment) combinations. Symbols indicate drug-paired lever responses differ from agonist/vehicle-infused controls (*p < 0.05, ***p < 0.001) or differs from naltrindole (p < 0.05) by Tukey’s HSD post-hoc tests.

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.
3.
Figure 3

Figure 3. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

(a) Reinstatement induced by 1 ng DAMGO is blocked by intra-NAc pretreatment with CTAP and not naltrindole. (b) Reinstatement induced by 300 ng DPDPE is blocked by intra-NAc pretreatment with naltrindole and not CTAP. (c) Reinstatement induced by intravenous cocaine priming (2 mg/kg) is blocked by intra-NAc pretreatment with CTAP and not naltrindole. Data represent the mean ± SEM agonist/antagonist combinations (n = 12–40 animals/treatment). Symbols indicate drug-paired lever responses differ from agonist/vehicle-infused controls (* p < 0.05, **p < 0.01) or CTAP differs from naltrindole (p < 0.05) by Tukey’s HSD post-hoc tests.

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.
4.
Figure 1

Figure 1. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

Intra-NAc infusions of (a) the mu-opioid receptor selective agonist DAMGO or (b) the delta-opioid receptor selective agonist DPDPE increase non-reinforced drug-paired lever responding in a within-session reinstatement procedure. Data represent the mean ± SEM for doses of DAMGO (n = 9–27 animals/treatment) and DPDPE (n = 5–22 animals/treatment). Symbols indicate drug-paired lever (* p < 0.05, **p < 0.01, ***p < 0.001) or inactive lever (††p < 0.001) differs from vehicle-infused controls by Dunnett’s post-hoc tests.

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.
5.
Figure 4

Figure 4. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

Intra-NAc infusion of (a) the endogenous opioid peptide β-endorphin dose-dependently reinstates drug-paired lever responding, (b) whereas met-enkephalin has no effect. (c) Intra-NAc infusion of the enkephalinase inhibitor thiorphan significantly increases drug-paired lever responding. Data represent the mean ± SEM for doses of β-endorphin (n = 10–15 animals/treatment), met-enkephalin (n = 7–11 animals/treatment), and thiorphan (n = 10–15 animals/treatment). Symbols indicate drug-paired lever (*p < 0.05, ***p < 0.001) or inactive lever (†††p < 0.001) differs from vehicle-infused controls by Dunnett’s post-hoc tests.

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.
6.
Figure 2

Figure 2. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

Intra-NAc pretreatment with (a) the mu-opioid receptor selective antagonist CTAP followed by 1 ng DAMGO and (b) the delta-opioid receptor selective antagonist naltrindol followed by 300 ng DPDPE dose-dependently attenuates reinstatement of cocaine seeking. Data represent the mean ± SEM for DAMGO/CTAP (n = 13–22 animals/treatment) and DPDPE/naltrindole (n =18–20 animals/treatment) combinations. Symbols indicate drug-paired lever (**p < 0.01, ***p ≤ 0.001) or inactive lever (p < 0.05) differs from agonist/vehicle-infused controls by Dunnett’s post-hoc tests.

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.
7.
Figure 6

Figure 6. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

(a) Effective NAc doses of DAMGO, β-endorphin and thiorphan are ineffective at reinstatement when infused in the CPu, while intra-CPu DPDPE induces significant drug-paired and inactive lever responding. (b) Pretreatment with intra-CPu infusions of CTAP has no effect on reinstatement induced by intravenous cocaine priming (2 mg/kg). Data represent the mean ± SEM for doses of agonists (n = 7–18 animals/treatment) and cocaine/antagonist (n = 6–8 animals/treatment) combinations. Symbols indicate drug-paired lever responses (**p < 0.01) or inactive lever responses (p < 0.05) differ from vehicle-infused controls by Dunnett’s post-hoc tests.

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.
8.
Figure 7

Figure 7. From: Role of Mu and Delta Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior.

Effects of reinstating doses of agonist treatments on horizontal locomotion in cocaine-trained animals. (a) Timeline of locomotor behavior during habituation for 2 h and following intra-NAc infusion of opioid agonist. (b) All agonists increase locomotor behavior for 1 h when infused in the NAc while β-endorphin activity remains elevated during the second h of testing. (c) Timeline of locomotor behavior in response to intra-CPu infusion of opioid agonists. (d) Only DPDPE and β-endorphin increased locomotor responding in the CPu with a trend for thiorphan to increase locomotion. Data represent the mean ± SEM for NAc (n = 7–13 animals/treatment) and CPu (n = 4–5 animals/treatment). Symbols indicate (*p < 0.05, ** p < 0.01, ***p < 0.001, p = 0.059) differs from vehicle-infused controls by Dunnett’s post-hoc tests.

Diana Simmons, et al. Neuropsychopharmacology. ;34(8):1946-1957.

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