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. 2011 Jul;216(2):219-33.
doi: 10.1007/s00213-011-2210-y. Epub 2011 Feb 12.

Effects of systemic or nucleus accumbens-directed dopamine D1 receptor antagonism on sucrose seeking in rats

Jeffrey W Grimm  1 , John H Harkness, Christine Ratliff, Jesse Barnes, Kindsey North, Stefan Collins
Affiliations

Effects of systemic or nucleus accumbens-directed dopamine D1 receptor antagonism on sucrose seeking in rats

Jeffrey W Grimm et al. Psychopharmacology (Berl). 2011 Jul.

Abstract

Rationale: Conditioned cues can elicit relapse to drug- and food-seeking behavior over prolonged periods of abstinence. If seeking behavior depends on mesolimbic dopamine D1 receptors, blocking these receptors should reduce seeking behavior.

Objectives: We examined the effects of either systemic or intra-nucleus accumbens administration of the D1 antagonist SCH 23390 on extinction responding (sucrose seeking) by rats either 1 or 30 days into forced abstinence.

Materials and methods: Rats self-administered 10% sucrose paired with a tone + light cue for 10 days. After either 1 or 30 days of forced abstinence, rats received systemic (0, 1, 5, or 25 μg/kg IP) or bilateral nucleus accumbens core or shell (0.3 or 0.6 μg/site) injections of SCH 23390 prior to extinction testing.

Results: Saline-treated rats responded more during extinction following 30 vs. 1 day of forced abstinence ("incubation of craving"). Systemic SCH 23390 reduced sucrose seeking after 1 day of forced abstinence, significantly reducing responding following pretreatment with 1, 5, and 25 μg/kg SCH 23390, but only 25 μg/kg significantly reduced sucrose seeking after 30 days of forced abstinence. SCH 23390 (0.3 or 0.6 μg/site) in the core or shell of the nucleus accumbens reduced sucrose seeking in all groups.

Conclusion: Nucleus accumbens D1 receptors are involved in sucrose seeking, but it is not clear if they are involved in the incubation of craving. The fact that D1 antagonism reduced sucrose seeking across an extended period of abstinence may be of use for development of treatment strategies for relapse.

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Conflict of interest statement

Conflict of interest The authors have no conflicts of interest or financial disclosures to report.

Figures

Fig. 1
Fig. 1
Active and inactive lever responding and locomotion following systemic injection with SCH 23390. Each bar represents a separate group of animals (n=8–12 per group). Means±SEMs are indicated on the figure. Asterisk indicates significant difference from 0 dose and dagger indicates significant difference from Day 1 group at that dose of SCH 23390, p<0.05
Fig. 2
Fig. 2
First 2 min active lever responding and locomotion following systemic injection with SCH 23390. Each bar represents a separate group of animals (n=8–12 per group). Means±SEMs are indicated on the figure. Dagger indicates significant overall difference from Day 1 groups, p<0.001
Fig. 3
Fig. 3
Active lever responses for sucrose following systemic injection with SCH 23390. Means±SEMs are indicated on the figure, n=18 per dose
Fig. 4
Fig. 4
Active and inactive lever responding and locomotion following microinjection with SCH 23390. Each bar represents a separate group of animals (n=9–11 per group). Means±SEMs are indicated on the figure. Asterisk indicates significant difference from 0 dose and dagger indicates significant difference from Day 1 group at that dose of SCH 23390, p’s<0.01
Fig. 5
Fig. 5
First 2 min active lever responding and locomotion following microinjection with SCH 23390. Each bar represents a separate group of animals (n=9–11 per group). Means±SEMs are indicated on the figure. Asterisk indicates significant difference from 0 dose and dagger indicates overall significant difference from Day 1 groups, p<0.05
Fig. 6
Fig. 6
Active lever responses for sucrose following microinjection with SCH 23390. Means±SEMs are indicated on the figure, n=8 per dose Core, and n=9 per dose Shell
Fig. 7
Fig. 7
Active and inactive lever responding and locomotion following microinjection with SCH 23390. Each bar represents a separate group of animals (n=11 per group). Means±SEMs are indicated on the figure. Asterisk indicates significant difference from Saline, p<0.05
Fig. 8
Fig. 8
Ranges of microinjection tip placements into the dorsal site, NAcc core, or NAcc shell. Anatomical plates were adapted from Paxinos and Watson (2007) and values indicate distance from bregma
Fig. 9
Fig. 9
Representative left hemisphere microinjection cannulae tracts and injector tip placements in the dorsal site (a), NAcc core (b), or NAcc shell (c); all placements in these examples were approximately +1.2 mm from bregma as identified in an atlas of the rat brain (Paxinos and Watson 2007). Landmarks identified are the anterior commissure (encircled) and the approximate location of the microinjection needle tip (+) for each micrograph. Scale bars represent 500 µm
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