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Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions.

Chambers RA, Sentir AM, Engleman EA - Psychopharmacology (Berl.) (2010)

Bottom Line: DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient.However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history.

View Article: PubMed Central - PubMed

Affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, 46202, USA. robchamb@iupui.edu

ABSTRACT

Rational: Exposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability.

Objective: This study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine.

Methods: Adult NVHL vs. SHAM-operated rats underwent a 5-day injection series of cocaine (15 mg/kg/day) vs. saline. One week later, rats were cannulated in nucleus accumbens SHELL, CORE, or caudate-putamen. Another week later, in vivo microdialysis sampled DA during locomotor testing in which a single cocaine injection (15 mg/kg) was delivered.

Results: NVHLs and cocaine history significantly increased behavioral activation approximately 2-fold over SHAM-saline history rats. DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient. However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.

Conclusion: Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history. These findings suggest other neurotransmitter systems, and alterations in striatal network function post-synaptic to DA transmission are more important to understanding the interactive effects of addictive drugs and mental illness.

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Related in: MedlinePlus

Experimental timeline according to animal age (post-natal day, PD)
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Fig1: Experimental timeline according to animal age (post-natal day, PD)

Mentions: Upon reaching adulthood (PD 60), rats were randomized to 5 days of once daily cocaine (15 mg/kg (NIDA) in 1 ml/kg saline i.p.) or saline injections (1 ml/kg i.p.) in home cages (Fig. 1). Two weeks later (PD 78), all rats underwent a single cocaine injection (15 mg/kg) within a 210-min locomotor arena session (under low red light) during microdialysis collection. Arenas () with 16 × 16 infrared beam detectors (Med Associates) were equipped with microdialysis tubing swivel arms mounted above the field with dual channel swivels (Instech). Microdialysis was conducted as previously described (Engleman et al. 2003). Dialysis tubing coursed from infusion pump-mounted syringes (Harvard Apparatus) through swivels to dialysis probes protected by a spring sheath (Instech). Outlet tubing coursed back through the swivel, terminating at the elbow of the swivel arm where dialysate was collected in microfuge tubes. Sessions began with hookup of probe tubing and securing of tethers to the dialysis sheath. Probes were perfused at 1.5 μl/min with aCSF containing (in millimolars) 140 NaCl, 3 KCl, 2.5 CaCl2, 1.0 MgCl2, 2.0 Na2PO4, and 0.2 ascorbate adjusted to pH 7.4 with 0.1 N NaOH. For the first 90 min of the 210-min session, rats habituated to the setup, followed by a 120-min recording phase measuring distance ambulated in 10-min bins. Cocaine injections were delivered at the 30-min point of the 120-min recording phase. Sixteen microdialysis samples (15 μl) were collected in 10 min intervals. Based on empirically verified flow rates and length of outlet tubing, these collections corresponded to four washout samples (during habituation), three baseline samples (pre-injection locomotion), and nine post-injection samples (post-injection locomotion).Fig. 1


Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions.

Chambers RA, Sentir AM, Engleman EA - Psychopharmacology (Berl.) (2010)

Experimental timeline according to animal age (post-natal day, PD)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2921051&req=5

Fig1: Experimental timeline according to animal age (post-natal day, PD)
Mentions: Upon reaching adulthood (PD 60), rats were randomized to 5 days of once daily cocaine (15 mg/kg (NIDA) in 1 ml/kg saline i.p.) or saline injections (1 ml/kg i.p.) in home cages (Fig. 1). Two weeks later (PD 78), all rats underwent a single cocaine injection (15 mg/kg) within a 210-min locomotor arena session (under low red light) during microdialysis collection. Arenas () with 16 × 16 infrared beam detectors (Med Associates) were equipped with microdialysis tubing swivel arms mounted above the field with dual channel swivels (Instech). Microdialysis was conducted as previously described (Engleman et al. 2003). Dialysis tubing coursed from infusion pump-mounted syringes (Harvard Apparatus) through swivels to dialysis probes protected by a spring sheath (Instech). Outlet tubing coursed back through the swivel, terminating at the elbow of the swivel arm where dialysate was collected in microfuge tubes. Sessions began with hookup of probe tubing and securing of tethers to the dialysis sheath. Probes were perfused at 1.5 μl/min with aCSF containing (in millimolars) 140 NaCl, 3 KCl, 2.5 CaCl2, 1.0 MgCl2, 2.0 Na2PO4, and 0.2 ascorbate adjusted to pH 7.4 with 0.1 N NaOH. For the first 90 min of the 210-min session, rats habituated to the setup, followed by a 120-min recording phase measuring distance ambulated in 10-min bins. Cocaine injections were delivered at the 30-min point of the 120-min recording phase. Sixteen microdialysis samples (15 μl) were collected in 10 min intervals. Based on empirically verified flow rates and length of outlet tubing, these collections corresponded to four washout samples (during habituation), three baseline samples (pre-injection locomotion), and nine post-injection samples (post-injection locomotion).Fig. 1

Bottom Line: DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient.However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history.

View Article: PubMed Central - PubMed

Affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, 46202, USA. robchamb@iupui.edu

ABSTRACT

Rational: Exposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability.

Objective: This study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine.

Methods: Adult NVHL vs. SHAM-operated rats underwent a 5-day injection series of cocaine (15 mg/kg/day) vs. saline. One week later, rats were cannulated in nucleus accumbens SHELL, CORE, or caudate-putamen. Another week later, in vivo microdialysis sampled DA during locomotor testing in which a single cocaine injection (15 mg/kg) was delivered.

Results: NVHLs and cocaine history significantly increased behavioral activation approximately 2-fold over SHAM-saline history rats. DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient. However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.

Conclusion: Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history. These findings suggest other neurotransmitter systems, and alterations in striatal network function post-synaptic to DA transmission are more important to understanding the interactive effects of addictive drugs and mental illness.

Show MeSH
Related in: MedlinePlus