There is strong evidence from animal studies with some support from human studies that 5HT systems are involved in cocaine use. The proposed research project is designed to investigate whether a group of cocaine dependent (CD) individuals display 5HT dysfunction as indicated by hormonal responses to meta-chlorophenylpiperazine (m-CPP) and platelet tritiated paroxetine binding and whether this group differs from other CD individuals in polymorphisms in genes for Serotonin Transporter (SERT) and tryptophan hydroxylase (TrPH) and clinical measures of impulsivity, aggression, craving and compulsive drug use. Furthermore, the project plans to determine if this particular group has a different outcome to treatment than other CD patients. Two hundred carefully screened subjects suffering from CD and volunteering for the study and a matched group of controls will be studied. After undergoing a comprehensive assessment and after 3 weeks of abstinence from cocaine, the subjects will undergo the m-CPP challenge in a double blind randomized design. Along with the hormonal responses to m-CPP, platelet tritiated paroxetine binding and polymorphisms in the genes for SERT and TrPH will be studied. The subjects will participate in 3 month intensive outpatient program and will be assessed on measures of outcome at the end of 3 months and after 6 months follow up. It is hypothesized that a group of CD subjects will display central 5HT dysfunction as indicated by a blunted hormonal response to m-CPP and reduced platelet tritiated paroxetine binding compared to other CD subjects and controls. Furthermore, it is also expected that this particular group of CD subjects will display polymorphisms in genes for SERT and TrPH and higher impulsivity, hostility, compulsive drug use and cocaine craving compared to the rest of CD subjects and controls. Finally, it is expected that this group will show a poorer outcome to treatment compared to other CD subjects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DA000340-02
Application #
2733481
Study Section
Special Emphasis Panel (ZDA1-KXN-G (11))
Project Start
1997-07-01
Project End
2002-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Patkar, Ashwin A; Mannelli, Paolo; Peindl, Kathleen et al. (2008) Relationship of the serotonin transporter with prolactin response to meta-chlorophenylpiperazine in cocaine dependence. J Psychiatr Res 42:1213-9
Patkar, Ashwin A; Mannelli, Paolo; Hill, Kevin P et al. (2006) Relationship of prolactin response to meta-chlorophenylpiperazine with severity of drug use in cocaine dependence. Hum Psychopharmacol 21:367-75
Patkar, Ashwin A; Batra, Vikas; Mannelli, Paolo et al. (2005) Medical symptoms associated with tobacco smoking with and without marijuana abuse among crack cocaine-dependent patients. Am J Addict 14:43-53
Smith, Rachel J; Doyle, Glenn A; Han, Angela M et al. (2005) Novel exonic mu-opioid receptor gene (OPRM1) polymorphisms not associated with opioid dependence. Am J Med Genet B Neuropsychiatr Genet 133B:105-9
Patkar, Ashwin A; Thornton, Charles C; Mannelli, Paolo et al. (2004) Comparison of pretreatment characteristics and treatment outcomes for alcohol-, cocaine-, and multisubstance-dependent patients. J Addict Dis 23:93-109
Patkar, Ashwin A; Berrettini, Wade H; Mannelli, Paolo et al. (2004) Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers. Psychiatr Genet 14:25-32
Patkar, Ashwin A; Murray, Heather W; Mannelli, Paolo et al. (2004) Pre-treatment measures of impulsivity, aggression and sensation seeking are associated with treatment outcome for African-American cocaine-dependent patients. J Addict Dis 23:109-22
Patkar, Ashwin A; Vergare, Michael J; Thornton, Charles C et al. (2003) Nicotine dependence and treatment outcome among African American cocaine-dependent patients. Nicotine Tob Res 5:411-8
Patkar, Ashwin A; Berrettini, Wade H; Lundy, Allan et al. (2003) Seasonal variations in the binding of [3H]paroxetine to the platelet serotonin transporter sites in African-American cocaine-dependent patients and healthy volunteers. Hum Psychopharmacol 18:103-11
Patkar, Ashwin A; Gottheil, Edward; Berrettini, Wade H et al. (2003) Relationship between platelet serotonin uptake sites and treatment outcome among African-American cocaine dependent individuals. J Addict Dis 22:79-92

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