Research Poster Draft MS edits -...
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Testosterone Positively Modulates Heroin Self-Administration Background and Objective § Epidemiological studies show men are more likely to engage in drug use, but women transition to problematic patterns of drug use more quickly, experience more problems with drug use, and are more likely to relapse than men 1,2 . § Preclinical studies in rats have shown that female rats exhibit greater levels of drug intake and greater levels of drug-seeking behavior than male rats 3,4 . § Studies show ovarian hormones are largely responsible for these differences between the sexes; increases in estrogen/estradiol levels increases drug self-administration 3,4 . § Little research has been done on the effects of testicular hormones on drug self-administration. No previous research studies have looked at the effects of testicular hormones on heroin self- administration. § This project will be the first empirical study of the effects of testosterone on heroin self-administration. Significant findings (in either direction) will reveal potential targets for substance abuse treatments. General Methods § Male, Longs-Evans rats, obtained during late adolescence, served as subjects. § One week after arrival, rats were placed on light food restriction and trained to press a lever for food reinforcement. § Training lasted one week and occurred daily in 2-hour sessions. § Rats received either a bilateral orchiectomy to remove both tests or received a sham orchiectomy where an incision was made, but the testes were not removed. § All rats were implanted with an intravenous catheter. § Rats were connected to an infusion pump through the intravenous catheter in a way that allows them free mobility in the chamber. ACKNOWLEDGEMENTS Funding for this study was provided by NIH Grant DA031725. The authors thank Meagan Thomas and Alexander Casimir for expert animal care and technical assistance. Self-Administration Procedure § Heroin self-administration training began 14 days after surgery. § For at least 7 days, each lever press produced a moderate dose of heroin (0.0075 mg/kg/infusion). § Following training, different doses of heroin were tested during each daily test session to generate a dose-effect curve showing drug intake over a 30-fold range of heroin. Longs-Evans Rat Andrew R. Peterson, Michael Zhang, Andrea Robinson, and Mark A. Smith Department of Psychology, Davidson College, Davidson NC 28035 1. Anker JJ, Carrol ME (2010). Females are more vulnerable to drug abuse than males: evidence from preclinical studies and the role of ovarian hormones. Current Topics in Behavioral Neurosciences, 8: 73-96. Doi: 10.1007/7854_2010_93 2. Brady KT, Randall CL (1999). Gender differences in substance use disorders. Psychiatric Clinics of North America, 22: 241-252. Doi: 10.1016/S0193-953X 3. Carroll ME, Anker JJ (2010). Sex differences and ovarian hormones in animal models of drug dependence. Hormones and Behavior, 58: 44-56. Doi: 10.1016/j.yhbeh.2009.10.001 4. Lynch WJ, Roth ME, Carroll ME (2002). Biological basis of sex differences in drug abuse: preclinical and clinical studies. Psychopharmacology, 164: 121-137. Doi: 10.1007/s00213-002-1183-2 Intravenous Catheter Rat Self-Administering Heroin Summary and Conclusions • Gonadectomized rats self-administered significantly less heroin than sham rats at all doses tested--resulting in a downward shift of the dose-effect curve. • No differences were observed in a saline substitution test, indicating that these differences were specific to the heroin stimulus. • These data suggest that endogenous testosterone positively modulates heroin self-administration and that androgenic hormones may increase heroin intake in males. Mean number of infusions on a fixed ratio (FR1) schedule of reinforcement. Heroin self-administration in sham (n = 5) and gonadectomized (GDX; n = 3) male rats during 2-hr sessions. ANOVA revealed main effects of dose and group. No significant differences were observed between groups during a saline substitution test or on inactive lever responding (data not shown.) Infusion Pump Self- Administration Apparatus References Results § Heroin self-administration was characterized by an inverted, U- shaped dose-effect curve in both groups. § Gonadectomized male rats self-administered significantly less heroin than intact male rats. Heroin (mg/kg/inf) SAL .0003 .001 .003 .01 .03 Number of Infusions / 2 hr 0 10 20 30 40 50 60 70 80 90 MALE GDX MALE SHAM
Transcript of Research Poster Draft MS edits -...
Testosterone Positively Modulates Heroin Self-Administration
Background and Objective
§ Epidemiological studies show men are more likely to engage in drug use, but women transition to problematic patterns of drug use more quickly, experience more problems with drug use, and are more likely to relapse than men1,2.
§ Preclinical studies in rats have shown that female rats exhibit greater levels of drug intake and greater levels of drug-seeking behavior than male rats3,4.§ Studies show ovarian hormones are largely responsible for these differences between the sexes; increases in estrogen/estradiol levels increases drug self-administration3,4.
§ Little research has been done on the effects of testicular hormones on drug self-administration. No previous research studies have looked at the effects of testicular hormones on heroin self-administration.
§ This project will be the first empirical study of the effects of testosterone on heroin self-administration. Significant findings (in either direction) will reveal potential targets for substance abuse treatments.
General Methods
§ Male, Longs-Evans rats, obtained during late adolescence, served as subjects.
§ One week after arrival, rats were placed on light food restriction and trained to press a lever for food reinforcement.
§ Training lasted one week and occurred daily in 2-hour sessions.
§ Rats received either a bilateral orchiectomy to remove both tests or received a sham orchiectomy where an incision was made, but the testes were not removed.
§ All rats were implanted with an intravenous catheter.
§ Rats were connected to an infusion pump through the intravenous catheter in a way that allows them free mobility in the chamber.
ACKNOWLEDGEMENTSFunding for this study was provided by NIH Grant DA031725. The authors thank Meagan Thomas and Alexander Casimir for expert animal care and technical assistance.
Self-Administration Procedure
§ Heroin self-administration training began 14 days after surgery.
§ For at least 7 days, each lever press produced a moderate dose of heroin (0.0075 mg/kg/infusion).
§ Following training, different doses of heroin were tested during each daily test session to generate a dose-effect curve showing drug intake over a 30-fold range of heroin.
Longs-Evans Rat
Andrew R. Peterson, Michael Zhang, Andrea Robinson, and Mark A. SmithDepartment of Psychology, Davidson College, Davidson NC 28035
1. Anker JJ, Carrol ME (2010). Females are more vulnerable to drug abuse than males: evidence from preclinical studies and the role of ovarian hormones. Current Topics in Behavioral Neurosciences, 8: 73-96. Doi: 10.1007/7854_2010_93
2. Brady KT, Randall CL (1999). Gender differences in substance use disorders. Psychiatric Clinics of North America, 22: 241-252. Doi: 10.1016/S0193-953X
3. Carroll ME, Anker JJ (2010). Sex differences and ovarian hormones in animal models of drug dependence. Hormones and Behavior, 58: 44-56. Doi: 10.1016/j.yhbeh.2009.10.001
4. Lynch WJ, Roth ME, Carroll ME (2002). Biological basis of sex differences in drug abuse: preclinical and clinical studies. Psychopharmacology, 164: 121-137. Doi: 10.1007/s00213-002-1183-2
Intravenous Catheter
Rat Self-Administering Heroin
Summary and Conclusions
• Gonadectomized rats self-administered significantly less heroin than sham rats at all doses tested--resulting in a downward shift of the dose-effect curve.
• No differences were observed in a saline substitution test, indicating that these differences were specific to the heroin stimulus.
• These data suggest that endogenous testosterone positively modulates heroin self-administration and that androgenic hormones may increase heroin intake in males.
Mean number of infusions on a fixed ratio (FR1) schedule of reinforcement. Heroin self-administration in sham (n = 5) and gonadectomized (GDX; n = 3) male rats during 2-hr sessions. ANOVA revealed main effects of dose and group. No significant differences were observed between groups during a saline substitution test or on inactive lever responding (data not shown.)
Infusion Pump
Self-Administration
Apparatus
References
Results
§ Heroin self-administration was characterized by an inverted, U-shaped dose-effect curve in both groups.
§ Gonadectomized male rats self-administered significantly less heroin than intact male rats.
Heroin (mg/kg/inf)SAL .0003 .001 .003 .01 .03
Num
ber o
f Inf
usio
ns /
2 hr
0
10
20
30
40
50
60
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80
90
MALE GDXMALE SHAM
