Individual differences in cocaine-induced locomotor activity in male Sprague–Dawley rats and their acquisition of and motivation to self-administer cocaine

Mandt, Bruce H.; Schenk, Susan; Zahniser, Nancy R.; Allen, Richard M.

doi:10.1007/s00213-008-1265-x

Cited by 41 publications

(72 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that the relationship between locomotor sensitization and sensitization to the effects of self-administered cocaine is unclear. Although some studies have found that prior noncontingent stimulant exposure decreases latency to acquisition and increases break points for cocaine (Schenk and Partridge, 2000;Suto et al, 2002), other studies (including our own LCR/HCR study) have found that cocaineinduced locomotor sensitization does not predict acquisition or break points (Lack et al, 2008;Mandt et al, 2008) and is dissociable from the motivational effects after compulsive cocaine consumption (Ahmed and Cador, 2006). Furthermore, noncontingent cocaine administration, such as that used to induce locomotor sensitization, is known under some conditions to produce different neurobiological effects than contingent cocaine administration (Chen et al, 2008;Miguéns et al, 2008).…”

Section: Discussionmentioning

confidence: 75%

“…One of the most consistent behavioral findings has been that rats with lower, but not higher, initial responsiveness to cocaine [low cocaine responders (LCRs), but not high cocaine responders (HCRs)] more readily develop cocaine-induced locomotor sensitization after repeated noncontingent cocaine (10 mg/kg i.p.) (Sabeti et al, 2003;Allen et al, 2007;Mandt et al, 2008Mandt et al, , 2009Nelson et al, 2009). It is noteworthy that the LCR/HCR difference in cocaine-induced locomotor sensitization was not found to predict acquisition of low-dose cocaine self-administration (Mandt et al, 2008).…”

Section: Introductionmentioning

confidence: 92%

“…(Sabeti et al, 2003;Allen et al, 2007;Mandt et al, 2008Mandt et al, , 2009Nelson et al, 2009). It is noteworthy that the LCR/HCR difference in cocaine-induced locomotor sensitization was not found to predict acquisition of low-dose cocaine self-administration (Mandt et al, 2008). However, whether LCRs and HCRs differ in the development of other forms of sensitization (e.g., during contingent cocaine selfadministration) remains unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cocaine Dose and Self-Administration History, but Not Initial Cocaine Locomotor Responsiveness, Affects Sensitization to the Motivational Effects of Cocaine in Rats

Mandt

Gomez²,

Johnston³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Cocaine addiction is a significant and complex disease. Part of this complexity is caused by the variability of the drug experience early in drug use (initial responsiveness, amount of use, etc.). In rats, individual differences in initial cocaine responsiveness and cocaine self-administration history both predict the development of cocaine sensitization, a putative mechanism contributing to the development of cocaine addiction. Here, we sought to determine the role of these factors and cocaine dose on the development of sensitization to cocaine's motivational effects during the earliest stages of self-administration. Rats were classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on acute cocaine-induced locomotor activity (10 mg/kg i.p.) before learning to self-administer cocaine (0.6 mg/kg/infusion i.v.) under a fixed ratio 1 (FR1) schedule of reinforcement. After acquisition, rats self-administered cocaine (0.6 or 1.2 mg/kg/infusion) under a progressive ratio (PR) schedule of reinforcement either immediately or after an additional five FR1 sessions (0.6 or 1.2 mg/kg/infusion). No LCR/HCR differences in sensitization were observed. However, regardless of LCR/HCR classification, exposure to the higher dose of cocaine produced sensitization to cocaine's motivational effects on the PR schedule (i.e., increased break points) and an escalation of consumption on the FR schedule. Thus, our results reveal a novel model for studying escalation and sensitization very early after acquisition and suggest that sensitization may be important in the earliest stages of the cocaine addiction process.

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cocaine Dose and Self-Administration History, but Not Initial Cocaine Locomotor Responsiveness, Affects Sensitization to the Motivational Effects of Cocaine in Rats

Mandt

Gomez²,

Johnston³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…(Sabeti et al, 2002(Sabeti et al, , 2003Gulley et al, 2003;Allen et al, 2007;Mandt et al, 2008). Brain cocaine levels and competing stereotyped behaviors do not explain the differential responsiveness of LCRs and HCRs to cocaine (Sabeti et al, 2002(Sabeti et al, , 2003Gulley et al, 2003).…”

mentioning

confidence: 89%

Low or High Cocaine Responding Rats Differ in Striatal Extracellular Dopamine Levels and Dopamine Transporter Number

Nelson

Larson

Zahniser

2009

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Both humans and animals exhibit marked individual differences in cocaine responsiveness. By using the median split of cocaine-induced locomotor activity, we have classified outbred male Sprague-Dawley rats as either low or high cocaine responders (LCRs or HCRs, respectively). LCR/HCR classification predicts differences in cocaine inhibition of striatal dopamine (DA) transporters (DATs), cocaine-induced locomotor sensitization, cocaine-conditioned place preference, and motivation to self-administer cocaine. In this study, we used in vivo microdialysis to investigate whether the differential cocaine inhibition of DATs in LCRs and HCRs is translated into differential extracellular DA levels. Paralleling their locomotor profiles, LCRs and HCRS had similar basal extracellular DA levels in dorsal striatum (dSTR) and nucleus accumbens (NAc); after acute cocaine injection (10 mg/kg i.p.), HCRs showed greater cocaine-induced increases in DA than LCRs, with more pronounced differences in NAc. After repeated cocaine injection, LCRs and HCRs no longer differed in cocaine-induced locomotor activity or extracellular DA. To further explore the differential susceptibility of LCR/HCR DATs to cocaine, we used in vitro [3 H]2-carbomethoxy-3-(4-fluorophenyl)tropane ([ 3 H]WIN 35,428) binding and quantitative autoradiography to measure the number of DAT binding sites and cocaine's affinity for them. After acute cocaine administration, HCRs had fewer DAT binding sites in dSTR and NAc shell, compared to LCRs. No LCR/ HCR differences were observed in DAT number after repeated cocaine injection or in cocaine's affinity. Our findings suggest that levels of striatal extracellular DA and DATs both make important contributions to initial differences in cocaine activation, which in LCRs/HCRs predict differential cocaine reward and reinforcement.

show abstract

“…This individual difference is linked to dopamine transporter (DAT) function (Sabeti et al, 2003;Briegleb et al, 2004) and cocaine CPP (Allen et al, 2007). However, in contrast to the HR/LR test, high cocaine responders do not differ from low cocaine responders in acquisition of cocaine self-administration (Mandt et al, 2008(Mandt et al, , 2012.…”

Section: Preclinical Behavioral Neuropharmacologymentioning

confidence: 99%

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

2013

View full text Add to dashboard Cite

Individual differences in cocaine-induced locomotor activity in male Sprague–Dawley rats and their acquisition of and motivation to self-administer cocaine

Cited by 41 publications

References 35 publications

Cocaine Dose and Self-Administration History, but Not Initial Cocaine Locomotor Responsiveness, Affects Sensitization to the Motivational Effects of Cocaine in Rats

Cocaine Dose and Self-Administration History, but Not Initial Cocaine Locomotor Responsiveness, Affects Sensitization to the Motivational Effects of Cocaine in Rats

Low or High Cocaine Responding Rats Differ in Striatal Extracellular Dopamine Levels and Dopamine Transporter Number

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

Contact Info

Product

Resources

About