My research is directed toward developing behavioral and pharmacological methods of reducing and preventing drug abuse. Animals are trained to self-administer drugs that humans abuse, and several phases of the addiction process are modeled, such as acquisition, maintenance, withdrawal, craving, and relapse. Our laboratory tests a number of therapeutic drugs, such as antidepressants and opioid and dopamine agonists and antagonists; they have shown considerable efficacy in reducing drug self-administration. Behavioral methods that are proving effective are enriching the environment with alternative nondrug reinforcers; for example, food and sweet-tasting drinking solutions. Behavioral economic analyses quantify the reinforcing efficacy of the drug under varied environmental and pharmacological treatments. Recent work shows that the greatest reduction in drug self-administration is achieved when behavioral and pharmacological treatments are combined. We are also interested in the interrelationships of feeding and drug abuse, and in testing the notion of common reward mechanisms for drugs, food, and other nondrug substances and events.
Another topic of study in our laboratory is the dependence producing effect of drugs. We have found that sensitive behavioral performance measures reveal subtle behavioral deficits due to drug withdrawal when no physical signs are present. Further, these behavioral deficits last for long periods of time, and may be a factor contributing to relapse to drug abuse in humans. Behavioral disturbances have been measured after low drug doses and short or intermittent periods of access with drugs such as caffeine, nicotine, cocaine, and phencyclidine (PCP), dispelling the common notion that excessive or long term drug abuse is necessary to produce withdrawal effects. We are using this model to find pharmacological and behavioral strategies to relieve withdrawal distress.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Swalve N, Smethells JR, Younk R, Mitchell J, Dougen B, Carroll ME. ex-specific attenuation of impulsive action by progesterone in a go/no-go task for cocaine in rats. Psychopharmacology (Berl). 2017 Oct 10. doi: 10.1007/s00213-017-4750-2.
- Martinez LA, Gross KS, Himmler BT, Emmitt NL, Peterson BM, Zlebnik NE, Foster Olive M, Carroll ME, Meisel RL, Mermelstein PG. Estradiol facilitation of cocaine self-administration in female rats requires activation of mGluR5. eNeuro. 2016;3(5). pii: ENEURO.0140-16.
- Smethells JR, Zlebnik NE, Miller DK, Will MJ, Booth F, Carroll ME. Cocaine self-administration and reinstatement in female rats selectively bred for high and low voluntary running. Drug Alcohol Depend. 2016;167:163-168.
- Swalve N, Smethells JR, Carroll ME. Sex differences in the acquisition and maintenance of cocaine and nicotine self-administration in rats. Psychopharmacology (Berl). 2016;233:1005-13.
- Radke AK, Zlebnik NE, Holtz NA, Carroll ME. Cocaine-induced reward enhancement measured with intracranial self-stimulation in rats bred for low versus high saccharin intake. Behav Pharmacol. 2016;27:133-136.
- Smethells JR, Swalve N, Brimijoin S, Gao Y, Parks RJ, Greer A, Carroll ME. Long-term blockade of cocaine self-administration and locomotor activation in rats by an adenoviral vector-delivered cocaine hydrolase. J Pharmacol Exp Ther. 2016;357:375-381.
- Carroll ME, Collins M, Kohl EA, Johnson S, Dougen B. Sex and menstrual cycle effects on chronic oral cocaine self-administration in rhesus monkeys: Effects of a nondrug alternative reward. Psychopharmacology (Berl). 2016;233(15-16):2973-84.
- Carroll ME, Lynch WD. How to study sex differences using animal models. Addict Biol. 2016;21:1007-29.
- Swalve N, Smethells JR, Carroll ME. Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine. Pharmacol Biochem Behav. 2016;145:17-23.
- Zlebnik NE, Carroll ME. Effects of the combination of wheel running and atomoxetine on cue- and cocaine-primed reinstatement in rats selected for high or low impulsivity. Psychopharmacology (Berl). 2015;232(6):1049-1059.
- Zlebnik NE, Carroll ME. Prevention of the incubation of cocaine seeking by aerobic exercise in female rats. Psychopharmacology (Berl). 2015;232:3507-13.
- Holtz NA, Radke AK, Zlebnik NE, Harris AC, Carroll ME. Intracranial self-stimulation reward thresholds during morphine withdrawal in rats bred for high (HiS) and low (LoS) saccharin intake. Brain Res. 2015;1602:119-126.
- Holtz NA, Carroll ME. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats. Behav Pharmacol. 2015 Jun;26(4):393-7.
- Smethells JR, Carroll ME. Discrepant effects of acute cocaine on impulsive choice (delay discounting) in female rats during an increasing- and adjusting-delay procedure. Psychopharmacology (Berl). 2015 Jul;232(14):2455-2462.
- Radke AK, Zlebnik NE, Carroll ME. Cocaine withdrawal in rats selectively bred for low (LoS) versus high (HiS) saccharin intake. Pharmacol Biochem Behav. 2014;29:51-55.
- Radke AK, Gewirtz JC, Carroll ME. Effects of age, but not sex, on elevated startle during withdrawal from acute morphine in adolescent and adult rats. Behav Pharmacol. 2015;26:485-8.
- Zlebnik NE, Hedges VL, Carroll ME, Meisel RL. Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats. Behav Brain Res. 2014;261:71-8
- Regier PS, Claxton AB, Zlebnik NE, Carroll ME. Cocaine-, caffeine-, and stress-evoked cocaine reinstatement in high vs. low impulsive rats: treatment with allopregnanolone. Drug Alcohol Depend. 2014;143:58-64.
- Zlebnik NE, Saykao AT, Carroll ME. Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats. Psychopharmacology (Berl). 2014;231:3787-98.
- Zlebnik NE, Brimijoin S, Gao Y, Saykao AT, Parks RJ, Carroll ME. Long-term reduction of cocaine self-administration in rats treated with adenoviral vector-delivered cocaine hydrolase: evidence for enzymatic activity. Neuropsychopharmacology. 2014;39(6):1538-1546.
- Holtz NA, Anker JJ, Regier PS, Claxton A, Carroll ME. Cocaine self-administration punished by i.v. histamine in rat models of high and low drug abuse vulnerability: effects of saccharin preference, impulsivity, and sex. Physiol Behav. 2013;122:32-8.
- Anker JJ, Brimijoin S, Gao Y, Geng L, Zlebnik NE, Parks RJ, Carroll ME. Cocaine hydrolase encoded in viral vector blocks the reinstatement of cocaine seeking in rats for 6 months. Biol Psychiatry. 2012;71(8):700-705.
- Holtz NA, Carroll ME. Baclofen has opposite effects on escalation of cocaine self-administration: increased intake in rats selectively bred for high (HiS) saccharin intake and decreased intake in those selected for low (LoS) saccharin intake. Pharmacol Biochem Behav. 2011;100(2):275-83.
- Holtz NA, Lozama A, Prisinzano TE, Carroll ME. Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone. Drug Alcohol Depend. 2012;120:233-7.
- Anker JJ, Carroll ME. Females are more vulnerable to drug abuse than males: evidence from preclinical studies and the role of ovarian hormones. Curr Top Behav Neurosci. 2011;8:73-96.
- Anker JJ, Carroll ME. Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake. Drug Alcohol Depend. 2011;118:68-72.
- Anker JJ, Zlebnik NE, Navin SF, Carroll ME. Responding during signaled availability and nonavailability of iv cocaine and food in rats: age and sex differences. Psychopharmacology (Berl). 2011;215(4):785-99.
- Carroll ME, Gao Y, Brimijoin S, Anker JJ. Effects of cocaine hydrolase on cocaine self-administration under a PR schedule and during extended access (escalation) in rats. Psychopharmacology (Berl). 2011;213(4):817-29.
Former Graduate Students:
Erin Larson (Ph.D. 2006, Neuroscience, University of Minnesota).
Natalie Zlebnik (Ph.D. 2014, Neuroscience, University of Minnesota).