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Cocaine-induced reinstatement of a conditioned place preference in developing rats: involvement of the d2 receptor.

Badanich KA, Kirstein CL - Brain Sci (2012)

Bottom Line: The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences.Adolescent rats (postnatal day (PND 28-39)) were trained to express a cocaine place preference.These data suggest intrinsic compensatory mechanisms in the mesolimbic DA pathway mediate responsivity to cocaine-induced reinstatement of a conditioned place preference during development.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, College of Arts and Sciences, University of South Florida Sarasota-Manatee, 8350 N. Tamiami Trail, Sarasota, FL 34243, USA. badanich@sar.usf.edu.

ABSTRACT
Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28-39)) were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement was determined by intra-VTA or intra-NAcc infusion of the DA D2 receptor antagonist sulpiride (100 μM) during a cocaine-primed reinstatement test (10 mg/kg cocaine, i.p.). Infusion of sulpiride into the VTA but not the NAcc blocked reinstatement of conditioned place preference. These data suggest intrinsic compensatory mechanisms in the mesolimbic DA pathway mediate responsivity to cocaine-induced reinstatement of a conditioned place preference during development.

No MeSH data available.


Related in: MedlinePlus

Dropsites for ventral tegmental area (VTA) and nucleus accumbens septi (NAcc) Injector Cannula. Placement of injector cannula into the NAcc and VTA. Dots represent the deepest portion of the injector cannula tip. Some dots represent more than one dropsite. (A) NAcc injector cannula placement in rats tested for reinstatement; n = 31. Plates = +2.20, +1.70 mm. (B) VTA injector cannula placement in rats tested for reinstatement; n = 32. Plates = −3.40 and −3.60 mm. Example photographs of injector placement are shown in the (C) NAcc and (D) VTA. Tip = bottom of injector tip, SN = substantia nigra, AC = anterior commissure.
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brainsci-02-00573-f001: Dropsites for ventral tegmental area (VTA) and nucleus accumbens septi (NAcc) Injector Cannula. Placement of injector cannula into the NAcc and VTA. Dots represent the deepest portion of the injector cannula tip. Some dots represent more than one dropsite. (A) NAcc injector cannula placement in rats tested for reinstatement; n = 31. Plates = +2.20, +1.70 mm. (B) VTA injector cannula placement in rats tested for reinstatement; n = 32. Plates = −3.40 and −3.60 mm. Example photographs of injector placement are shown in the (C) NAcc and (D) VTA. Tip = bottom of injector tip, SN = substantia nigra, AC = anterior commissure.

Mentions: Phase 3: Surgical Procedures. Our lab has consistently used weight based coordinates to aim microdialysis guide cannula at the NAcc of adolescent rats due to the fact that adolescents rapidly grow in size and gain a substantial amount of weight during development that ultimately affects accurate placement of microdialysis probes in target brain regions [3,18,34,35,36,37] and the VTA [38]. Since our previous microdialysis experiments have also included adult comparisons, we have observed using these weight based coordinates for adult rats provide much greater accuracy in placing cannula in both the NAcc and VTA for adult rats as well. Therefore, weight based coordinates were used for adult rats in the present experiments. On PND 65, rats were anesthetized with ketamine/xylazine (75 mg/kg ketamine, 5 mg/kg xylazine, i.p.), an incision was made over the skull and the rat was mounted on a stereotaxic instrument for surgery (myNeurolab, St Louis, MO). Specifically for NAcc cannula placements, the head was leveled and holes for bilateral guide cannula were drilled in the skull at a site above the NAcc (Plastics One, 10.5 mm guides, 22 gauge, 1.5 mm separation). Two holes for skull screws were drilled in the skull adjacent to the guide cannula as well. A guide cannula equipped with a dummy cannula (for CMA 11 probes; outer diameter 0.6 mm) was lowered into the brain to a site just above the anterior NAcc (mean weight based coordinate measured from bregma: anterior (+2.3); lateral (+0.7); ventral (−5.6)) and affixed to the skull with cranioplast. The dorsal-ventral coordinate for NAcc coordinates were measured from the skull surface and allowed room for later insertion of the 2mm microinjection tip. During histology (see below), NAcc guide cannula dropsites were compared to Paxinos and Watson’s rat brain atlas [39] for verification of proper placement in the NAcc. For VTA cannula placements, weight-based coordinates were generated according to Pellegrino, Pellegrino and Cushman [40]. Specifically, rats were placed in the stereotax so that the interaural line was 5.0 mm below the upper incisor bar. Holes for bilateral guide cannula were drilled in the skull at a site above the VTA (Plastics One, 10.5 mm guides, 22 gauge, 2.0 mm separation). Two holes for skull screws were drilled in the skull adjacent to the guide cannula as well. A guide cannula equipped with a dummy cannula (for CMA 11 probes; outer diameter 0.6 mm) was lowered into the brain to a site just above the VTA [from bregma: posterior (−3.5); lateral (+1.0); ventral (−6.0)] and affixed to the skull with cranioplast. The dorsal-ventral coordinate for NAcc coordinates were measured from the skull surface and allowed room for later insertion of the 2 mm microinjection tip. During histology (see below), VTA guide cannula dropsites were compared to Pellegrino, Pellegrino and Cushman’s rat brain atlas [40] for verification of proper placement in the VTA. Note that NAcc and VTA coordinates listed above are averages given that weight based coordinates were used [34,38]. It should be noted that the anterior NAcc was specifically targeted given its suggested role in incentive salience [41]. Furthermore, we specifically hit the PN & PBP nuclei of the VTA because these nuclei send projections to the NAcc. These two nuclei are located primarily in the anterior portion of the VTA. Guide cannulae placements for the VTA and NAcc are illustrated with example photographs in Figure 1. Following surgery, rats were singly housed in the home cage and allowed at least 4 days for recovery.


Cocaine-induced reinstatement of a conditioned place preference in developing rats: involvement of the d2 receptor.

Badanich KA, Kirstein CL - Brain Sci (2012)

Dropsites for ventral tegmental area (VTA) and nucleus accumbens septi (NAcc) Injector Cannula. Placement of injector cannula into the NAcc and VTA. Dots represent the deepest portion of the injector cannula tip. Some dots represent more than one dropsite. (A) NAcc injector cannula placement in rats tested for reinstatement; n = 31. Plates = +2.20, +1.70 mm. (B) VTA injector cannula placement in rats tested for reinstatement; n = 32. Plates = −3.40 and −3.60 mm. Example photographs of injector placement are shown in the (C) NAcc and (D) VTA. Tip = bottom of injector tip, SN = substantia nigra, AC = anterior commissure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061817&req=5

brainsci-02-00573-f001: Dropsites for ventral tegmental area (VTA) and nucleus accumbens septi (NAcc) Injector Cannula. Placement of injector cannula into the NAcc and VTA. Dots represent the deepest portion of the injector cannula tip. Some dots represent more than one dropsite. (A) NAcc injector cannula placement in rats tested for reinstatement; n = 31. Plates = +2.20, +1.70 mm. (B) VTA injector cannula placement in rats tested for reinstatement; n = 32. Plates = −3.40 and −3.60 mm. Example photographs of injector placement are shown in the (C) NAcc and (D) VTA. Tip = bottom of injector tip, SN = substantia nigra, AC = anterior commissure.
Mentions: Phase 3: Surgical Procedures. Our lab has consistently used weight based coordinates to aim microdialysis guide cannula at the NAcc of adolescent rats due to the fact that adolescents rapidly grow in size and gain a substantial amount of weight during development that ultimately affects accurate placement of microdialysis probes in target brain regions [3,18,34,35,36,37] and the VTA [38]. Since our previous microdialysis experiments have also included adult comparisons, we have observed using these weight based coordinates for adult rats provide much greater accuracy in placing cannula in both the NAcc and VTA for adult rats as well. Therefore, weight based coordinates were used for adult rats in the present experiments. On PND 65, rats were anesthetized with ketamine/xylazine (75 mg/kg ketamine, 5 mg/kg xylazine, i.p.), an incision was made over the skull and the rat was mounted on a stereotaxic instrument for surgery (myNeurolab, St Louis, MO). Specifically for NAcc cannula placements, the head was leveled and holes for bilateral guide cannula were drilled in the skull at a site above the NAcc (Plastics One, 10.5 mm guides, 22 gauge, 1.5 mm separation). Two holes for skull screws were drilled in the skull adjacent to the guide cannula as well. A guide cannula equipped with a dummy cannula (for CMA 11 probes; outer diameter 0.6 mm) was lowered into the brain to a site just above the anterior NAcc (mean weight based coordinate measured from bregma: anterior (+2.3); lateral (+0.7); ventral (−5.6)) and affixed to the skull with cranioplast. The dorsal-ventral coordinate for NAcc coordinates were measured from the skull surface and allowed room for later insertion of the 2mm microinjection tip. During histology (see below), NAcc guide cannula dropsites were compared to Paxinos and Watson’s rat brain atlas [39] for verification of proper placement in the NAcc. For VTA cannula placements, weight-based coordinates were generated according to Pellegrino, Pellegrino and Cushman [40]. Specifically, rats were placed in the stereotax so that the interaural line was 5.0 mm below the upper incisor bar. Holes for bilateral guide cannula were drilled in the skull at a site above the VTA (Plastics One, 10.5 mm guides, 22 gauge, 2.0 mm separation). Two holes for skull screws were drilled in the skull adjacent to the guide cannula as well. A guide cannula equipped with a dummy cannula (for CMA 11 probes; outer diameter 0.6 mm) was lowered into the brain to a site just above the VTA [from bregma: posterior (−3.5); lateral (+1.0); ventral (−6.0)] and affixed to the skull with cranioplast. The dorsal-ventral coordinate for NAcc coordinates were measured from the skull surface and allowed room for later insertion of the 2 mm microinjection tip. During histology (see below), VTA guide cannula dropsites were compared to Pellegrino, Pellegrino and Cushman’s rat brain atlas [40] for verification of proper placement in the VTA. Note that NAcc and VTA coordinates listed above are averages given that weight based coordinates were used [34,38]. It should be noted that the anterior NAcc was specifically targeted given its suggested role in incentive salience [41]. Furthermore, we specifically hit the PN & PBP nuclei of the VTA because these nuclei send projections to the NAcc. These two nuclei are located primarily in the anterior portion of the VTA. Guide cannulae placements for the VTA and NAcc are illustrated with example photographs in Figure 1. Following surgery, rats were singly housed in the home cage and allowed at least 4 days for recovery.

Bottom Line: The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences.Adolescent rats (postnatal day (PND 28-39)) were trained to express a cocaine place preference.These data suggest intrinsic compensatory mechanisms in the mesolimbic DA pathway mediate responsivity to cocaine-induced reinstatement of a conditioned place preference during development.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, College of Arts and Sciences, University of South Florida Sarasota-Manatee, 8350 N. Tamiami Trail, Sarasota, FL 34243, USA. badanich@sar.usf.edu.

ABSTRACT
Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28-39)) were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement was determined by intra-VTA or intra-NAcc infusion of the DA D2 receptor antagonist sulpiride (100 μM) during a cocaine-primed reinstatement test (10 mg/kg cocaine, i.p.). Infusion of sulpiride into the VTA but not the NAcc blocked reinstatement of conditioned place preference. These data suggest intrinsic compensatory mechanisms in the mesolimbic DA pathway mediate responsivity to cocaine-induced reinstatement of a conditioned place preference during development.

No MeSH data available.


Related in: MedlinePlus