The role of the mesolimbic dopamine (DA) pathway (specifically the nucleus accumbens septi. NAcc) in reward has been well-documented in adult animals. Drugs of abuse, such as cocaine increase DA levels in the NAcc of adult rats. Similarly, in many studies drug """"""""expectancy"""""""" or anticipation has been shown to increase accumbal DA in the adult. As a result, several studies have implicated this pathway as a neural substrate mediating drug abuse. In humans, drug abuse is often established in adolescence not adulthood: this is especially true of cocaine, Unfortunately, few studies have examined changes in the NAcc in response to cocaine during adolescence. Studying the functional responsiveness of this reward system and the effects of cocaine during adolescence is critical. The data show that drug use begins around adolescence and continues into adulthood. Moreover, development of the brain is still ongoing during this period, and the DA system may be critically altered by cocaine exposure. To this end, we modified and adapted the in vivo microdialysis procedure to enable us to effectively and reliably recover DA from the NAcc of young rats. The dialysis procedure allows measurement of the neurochemical changes resulting from cocaine. The present studies propose to use microdialysis to examine the effects of acute, repeated or """"""""expected"""""""" cocaine on the NAcc in preadolescent (postnatal day 25; PND 25), periadolescent (PND 35, 45) and adult (PND 60) animals. Additionally, behavioral studies will assess responsiveness to cocaine using a conditioned place preference (CPP) paradigm and novelty-seeking behavior to assess age-related vulnerability to cocaine's effects. Finally, we propose to examine the effects of repeated cocaine at these critical ages on functioning of the adult DA system. The principal goals of the proposed studies are to: first, determine the effects of acute, repeated or """"""""expected"""""""" cocaine on mesolimbic DA in PND 25, 35, 45 and 60 rats; second, establish CPP across age; third, measure novelty-seeking differences across age and DA activity in high vs. low responders and finally, determine effects of cocaine exposure during critical periods of adolescence on later DA responsiveness. It is our basic hypothesis that periadolescent animals are unique in their response to cocaine and that repeated administration during this time might down-regulate the basal functioning of this developing system but increase responsiveness to subsequent drug administration and therefore drive repeated drug use. The proposed studies will allow us to examine the underlying mechanism of cocaine's effects in adolescence which is critical in order to understand how these processes control the initiation and maintenance of cocaine abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA014024-03S1
Application #
6800280
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Pilotte, Nancy S
Project Start
2001-09-30
Project End
2006-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
3
Fiscal Year
2003
Total Cost
$7,975
Indirect Cost
Name
University of South Florida
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
069687242
City
Tampa
State
FL
Country
United States
Zip Code
33612
Tignanelli, Christopher J; Herrera Loeza, Silvia G; Yeh, Jen Jen (2014) KRAS and PIK3CA mutation frequencies in patient-derived xenograft models of pancreatic and colorectal cancer are reflective of patient tumors and stable across passages. Am Surg 80:873-7
Sponaugle, Ashley E; Badanich, Kimberly A; Kirstein, Cheryl L (2008) Localization of stereotaxic coordinates for the ventral tegmental area in early adolescent, mid-adolescent and adult rats. Brain Res 1218:215-23
Badanich, Kimberly A; Maldonado, Antoniette M; Kirstein, Cheryl L (2008) Early adolescents show enhanced acute cocaine-induced locomotor activity in comparison to late adolescent and adult rats. Dev Psychobiol 50:127-33
Catlow, Briony J; Kirstein, Cheryl L (2007) Cocaine during adolescence enhances dopamine in response to a natural reinforcer. Neurotoxicol Teratol 29:57-65
Stansfield, Kirstie H; Kirstein, Cheryl L (2006) Effects of novelty on behavior in the adolescent and adult rat. Dev Psychobiol 48:10-5
Badanich, Kimberly A; Adler, Kristopher J; Kirstein, Cheryl L (2006) Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi. Eur J Pharmacol 550:95-106
Maldonado, Antoniette M; Kirstein, Cheryl L (2005) Handling alters cocaine-induced activity in adolescent but not adult male rats. Physiol Behav 84:321-6
Catlow, Briony J; Kirstein, Cheryl L (2005) Heightened cocaine-induced locomotor activity in adolescent compared to adult female rats. J Psychopharmacol 19:443-7
Maldonado, Antoniette M; Kirstein, Cheryl L (2005) Cocaine-induced locomotor activity is increased by prior handling in adolescent but not adult female rats. Physiol Behav 86:568-72
Vila, J L; Philpot, R M; Kirstein, C L (2004) Grid crossing: inability to compare activity levels between adolescent and adult rats. Ann N Y Acad Sci 1021:418-21

Showing the most recent 10 out of 11 publications