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Responding during signaled availability and nonavailability of iv cocaine and food in rats: age and sex differences

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Abstract

Rationale

Research suggests that age and sex are vulnerability factors for drug abuse. However, few studies have systematically examined their interaction.

Objective

The purpose of the present study was to examine male and female, adult and adolescent rats under a procedure that measures responding during periods of signaled availability and nonavailability of iv cocaine and food reinforcers.

Methods

Adolescent and adult rats lever pressed for iv infusions of cocaine or food pellets under a procedure with three components of signaled availability of the reinforcer alternating with two components of signaled nonavailability. Adolescent rats were removed and then later retested under the same conditions as adults, and a group of adult rats was also removed and retested after a similar number of days. A subset of rats earning cocaine infusions under the initial test was later retested with food pellets under the same behavioral task to assess the influence of prior cocaine exposure on subsequent responding for a nondrug reinforcer.

Results

Adolescents (vs. adults) made more responses during periods of signaled iv cocaine availability and nonavailabiltiy, and adult females responded more than adult males during these periods. Responding during periods of signaled nonavailability of iv cocaine and food did not differ between the initial and subsequent retest conditions in adult rats. Further, adult males and females exposed to cocaine during adolescence responded more during periods of food availability compared to cocaine-naïve adults.

Conclusion

These results indicate that sex and age are vulnerability factors in cocaine abuse, and cocaine exposure during critical developmental stages can have long-lasting effects.

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References

  • Adriani W, Laviola G (2003) Elevated levels of impulsivity and reduced place conditioning with d-amphetamine: two behavioral features of adolescence in mice. Behav Neurosci 117:695–703

    Article  PubMed  CAS  Google Scholar 

  • Anker JJ, Carroll ME (2010a) Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats. Psychopharmacol Berl 208:211–222

    Article  CAS  Google Scholar 

  • Anker JJ, Carroll ME (2010b) Sex differences in the effects of allopregnanolone on yohimbine-induced reinstatement of cocaine seeking in rats. Drug Alcohol Depend 107:264–267

    Article  PubMed  CAS  Google Scholar 

  • Anker JJ, Gliddon LA, Carroll ME (2008) Impulsivity on a Go/No-go task for intravenous cocaine or food in male and female rats selectively bred for high and low saccharin intake. Behav Pharmacol 19:615–629

    Article  PubMed  CAS  Google Scholar 

  • Arroyo M, Markou A, Robbins TW, Everitt BJ (1998) Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine. Psychopharmacol Berl 140:331–344

    Article  CAS  Google Scholar 

  • Badanich KA, Maldonado AM, Kirstein CL (2008) Early adolescents show enhanced acute cocaine-induced locomotor activity in comparison to late adolescent and adult rats. Dev Psychobiol 50:127–133

    Article  PubMed  CAS  Google Scholar 

  • Badia-Elder N, Kiefer SW, Dess NK (1996) Taste reactivity in rats selectively bred for high vs. low saccharin consumption. Physiol Behav 59:749–755

    Article  PubMed  CAS  Google Scholar 

  • Becker JB, Hu M (2008) Sex differences in drug abuse. Front Neuroendocrinol 29:36–47

    Article  PubMed  CAS  Google Scholar 

  • Bolanos CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ (2003) Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood. Biol Psychiatry 54:1317–1329

    Article  PubMed  CAS  Google Scholar 

  • Bolanos CA, Willey MD, Maffeo ML, Powers KD, Kinka DW, Grausam KB, Henderson RP (2008) Antidepressant treatment can normalize adult behavioral deficits induced by early-life exposure to methylphenidate. Biol Psychiatry 63:309–316

    Article  PubMed  CAS  Google Scholar 

  • Brandon CL, Marinelli M, Baker LK, White FJ (2001) Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats. Neuropsychopharmacology 25:651–661

    Article  PubMed  CAS  Google Scholar 

  • Brandon CL, Marinelli M, White FJ (2003) Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons. Biol Psychiatry 54:1338–1344

    Article  PubMed  CAS  Google Scholar 

  • Brenhouse HC, Andersen SL (2008) Delayed extinction and stronger reinstatement of cocaine conditioned place preference in adolescent rats, compared to adults. Behav Neurosci 122:460–465

    Article  PubMed  CAS  Google Scholar 

  • Brenhouse HC, Sonntag KC, Andersen SL (2008) Transient D1 dopamine receptor expression on prefrontal cortex projection neurons: relationship to enhanced motivational salience of drug cues in adolescence. J Neurosci 28:2375–2382

    Article  PubMed  CAS  Google Scholar 

  • Brunswick AF, Messeri P (1986) Drugs, lifestyle, and health: a longitudinal study of urban black youth. Am J Public Health 76:52–57

    Article  PubMed  CAS  Google Scholar 

  • Burton CL, Nobrega JN, Fletcher PJ (2010) The effects of adolescent methylphenidate self-administration on responding for a conditioned reward, amphetamine-induced locomotor activity, and neuronal activation. Psychopharmacol Berl 208:455–468

    Article  CAS  Google Scholar 

  • Carlezon WA Jr, Mague SD, Andersen SL (2003) Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry 54:1330–1337

    Article  PubMed  CAS  Google Scholar 

  • Carroll ME, Boe IN (1982) Increased intravenous drug self-administration during deprivation of other reinforcers. Pharmacol Biochem Behav 17:563–567

    Article  PubMed  CAS  Google Scholar 

  • Carroll ME, Anker JJ (2010) Sex differences and ovarian hormones in animal models of drug dependence. Horm Behav 58:44–56

    Article  PubMed  CAS  Google Scholar 

  • Carroll ME, Morgan AD, Lynch WJ, Campbell UC, Dess NK (2002) Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences. Psychopharmacol Berl 161:304–313

    Article  CAS  Google Scholar 

  • Carroll ME, Morgan AD, Anker JJ, Perry JL, Dess NK (2008) Selective breeding for differential saccharin intake as an animal model of drug abuse. Behav Pharmacol 19:435–460

    Article  PubMed  CAS  Google Scholar 

  • Carroll ME, Anker JJ, Perry JL (2009) Modeling risk factors for nicotine and other drug abuse in the preclinical laboratory. Drug Alcohol Depend 104(Suppl 1):S70–S78

    Article  PubMed  CAS  Google Scholar 

  • Casey BJ, Getz S, Galvan A (2008) The adolescent brain. Dev Rev 28:62–77

    PubMed  Google Scholar 

  • Caster JM, Walker QD, Kuhn CM (2005) Enhanced behavioral response to repeated-dose cocaine in adolescent rats. Psychopharmacol Berl 183:218–225

    Article  CAS  Google Scholar 

  • Caster JM, Walker QD, Kuhn CM (2007) A single high dose of cocaine induces differential sensitization to specific behaviors across adolescence. Psychopharmacol Berl 193:247–260

    Article  CAS  Google Scholar 

  • Chen H, Matta SG, Sharp BM (2007) Acquisition of nicotine self-administration in adolescent rats given prolonged access to the drug. Neuropsychopharmacology 32:700–709

    Article  PubMed  CAS  Google Scholar 

  • Chen K, Kandel D (2002) Relationship between extent of cocaine use and dependence among adolescents and adults in the United States. Drug Alcohol Depend 68:65–85

    Article  PubMed  Google Scholar 

  • Chung T, Maisto SA (2006) Relapse to alcohol and other drug use in treated adolescents: review and reconsideration of relapse as a change point in clinical course. Clin Psychol Rev 26:149–161

    Article  PubMed  Google Scholar 

  • Craft RM (2008) Sex differences in analgesic, reinforcing, discriminative, and motoric effects of opioids. Exp Clin Psychopharmacol 16:376–385

    Article  PubMed  CAS  Google Scholar 

  • Crawford CA, Villafranca SW, Cyr MC, Farley CM, Reichel CM, Gheorghe SL, Krall CM, McDougall SA (2007) Effects of early methylphenidate exposure on morphine- and sucrose-reinforced behaviors in adult rats: relationship to dopamine D2 receptors. Brain Res 1139:245–253

    Article  PubMed  CAS  Google Scholar 

  • Dennis M, Godley SH, Diamond G, Tims FM, Babor T, Donaldson J, Liddle H, Titus JC, Kaminer Y, Webb C, Hamilton N, Funk R (2004) The Cannabis Youth Treatment (CYT) study: main findings from two randomized trials. J Subst Abuse Treat 27:197–213

    Article  PubMed  Google Scholar 

  • Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305:1014–1017

    Article  PubMed  CAS  Google Scholar 

  • Ersche KD, Roiser JP, Robbins TW, Sahakian BJ (2008) Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans. Psychopharmacol Berl 197:421–431

    Article  CAS  Google Scholar 

  • Ferguson SA, Boctor SY (2010) Cocaine responsiveness or anhedonia in rats treated with methylphenidate during adolescence. Neurotoxicol Teratol 32:432–442

    Article  PubMed  CAS  Google Scholar 

  • Fullgrabe MW, Vengeliene V, Spanagel R (2007) Influence of age at drinking onset on the alcohol deprivation effect and stress-induced drinking in female rats. Pharmacol Biochem Behav 86:320–326

    Article  PubMed  Google Scholar 

  • Geier CF, Terwilliger R, Teslovich T, Velanova K, Luna B (2010) Immaturities in reward processing and its influence on inhibitory control in adolescence. Cereb Cortex 20:1613–1629

    Article  PubMed  CAS  Google Scholar 

  • Griggs R, Weir C, Wayman W, Koeltzow TE (2010) Intermittent methylphenidate during adolescent development produces locomotor hyperactivity and an enhanced response to cocaine compared to continuous treatment in rats. Pharmacol Biochem Behav 96:166–174

    Article  PubMed  CAS  Google Scholar 

  • Guerriero RM, Hayes MM, Dhaliwal SK, Ren JQ, Kosofsky BE (2006) Preadolescent methylphenidate versus cocaine treatment differ in the expression of cocaine-induced locomotor sensitization during adolescence and adulthood. Biol Psychiatry 60:1171–1180

    Article  PubMed  CAS  Google Scholar 

  • Ignjatova L, Raleva M (2009) Gender difference in the treatment outcome of patients served in the mixed-gender program. Bratisl Lek Listy 110:285–289

    PubMed  CAS  Google Scholar 

  • Jackson LR, Robinson TE, Becker JB (2006) Sex differences and hormonal influences on acquisition of cocaine self-administration in rats. Neuropsychopharmacology 31:129–138

    PubMed  CAS  Google Scholar 

  • Kantak KM, Goodrich CM, Uribe V (2007) Influence of sex, estrous cycle, and drug-onset age on cocaine self-administration in rats (Rattus norvegicus). Exp Clin Psychopharmacol 15:37–47

    Article  PubMed  CAS  Google Scholar 

  • Kerstetter KA, Kantak KM (2007) Differential effects of self-administered cocaine in adolescent and adult rats on stimulus-reward learning. Psychopharmacol Berl 194:403–411

    Article  CAS  Google Scholar 

  • Kerstetter KA, Aguilar VR, Parrish AB, Kippin TE (2008) Protracted time-dependent increases in cocaine-seeking behavior during cocaine withdrawal in female relative to male rats. Psychopharmacol Berl 198:63–75

    Article  CAS  Google Scholar 

  • Levin ED, Lawrence SS, Petro A, Horton K, Rezvani AH, Seidler FJ, Slotkin TA (2007) Adolescent vs. adult-onset nicotine self-administration in male rats: duration of effect and differential nicotinic receptor correlates. Neurotoxicol Teratol 29:458–465

    Article  PubMed  CAS  Google Scholar 

  • Li C, Frantz KJ (2009) Attenuated incubation of cocaine seeking in male rats trained to self-administer cocaine during periadolescence. Psychopharmacol Berl 204:725–733

    Article  CAS  Google Scholar 

  • Lopez B, Turner RJ, Saavedra LM (2005) Anxiety and risk for substance dependence among late adolescents/young adults. J Anxiety Disord 19:275–294

    Article  PubMed  Google Scholar 

  • Lynch WJ (2006) Sex differences in vulnerability to drug self-administration. Exp Clin Psychopharmacol 14:34–41

    Article  PubMed  CAS  Google Scholar 

  • Lynch WJ (2008) Acquisition and maintenance of cocaine self-administration in adolescent rats: effects of sex and gonadal hormones. Psychopharmacol Berl 197:237–246

    Article  CAS  Google Scholar 

  • Lynch WJ (2009) Sex and ovarian hormones influence vulnerability and motivation for nicotine during adolescence in rats. Pharmacol Biochem Behav 94:43–50

    Article  PubMed  CAS  Google Scholar 

  • Lynch WJ, Carroll ME (1999) Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats. Psychopharmacol Berl 144:77–82

    Article  CAS  Google Scholar 

  • Lynch WJ, Carroll ME (2000) Reinstatement of cocaine self-administration in rats: sex differences. Psychopharmacol Berl 148:196–200

    Article  CAS  Google Scholar 

  • Mann K, Ackermann K, Croissant B, Mundle G, Nakovics H, Diehl A (2005) Neuroimaging of gender differences in alcohol dependence: are women more vulnerable? Alcohol Clin Exp Res 29:896–901

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (2003) Guidelines for the care and use of mammals in neuroscience and behavioral research. National Academies, Washington, p 209

    Google Scholar 

  • Newcomb MD, Bentler PM (1987) The impact of late adolescent substance use on young adult health status and utilization of health services: a structural-equation model over four years. Soc Sci Med 24:71–82

    Article  PubMed  CAS  Google Scholar 

  • Ojeda SR, Andrews WW, Advis JP, White SS (1980) Recent advances in the endocrinology of puberty. Endocr Rev 1:228–257

    Article  PubMed  CAS  Google Scholar 

  • Parylak SL, Caster JM, Walker QD, Kuhn CM (2008) Gonadal steroids mediate the opposite changes in cocaine-induced locomotion across adolescence in male and female rats. Pharmacol Biochem Behav 89:314–323

    Article  PubMed  CAS  Google Scholar 

  • Perepletchikova F, Krystal JH, Kaufman J (2008) Practitioner review: adolescent alcohol use disorders: assessment and treatment issues. J Child Psychol Psychiatry 49:1131–1154

    PubMed  Google Scholar 

  • Perry JL, Anderson MM, Nelson SE, Carroll ME (2007) Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake. Physiol Behav 91:126–133

    Article  PubMed  CAS  Google Scholar 

  • Randall CL, Roberts JS, Del Boca FK, Carroll KM, Connors GJ, Mattson ME (1999) Telesco** of landmark events associated with drinking: a gender comparison. J Stud Alcohol 60:252–260

    PubMed  CAS  Google Scholar 

  • Rao U, Ryan ND, Dahl RE, Birmaher B, Rao R, Williamson DE, Perel JM (1999) Factors associated with the development of substance use disorder in depressed adolescents. J Am Acad Child Adolesc Psychiatry 38:1109–1117

    Article  PubMed  CAS  Google Scholar 

  • Roth ME, Carroll ME (2004) Sex differences in the escalation of intravenous cocaine intake following long- or short-access to cocaine self-administration. Pharmacol Biochem Behav 78:199–207

    Article  PubMed  CAS  Google Scholar 

  • Roth ME, Cosgrove KP, Carroll ME (2004) Sex differences in the vulnerability to drug abuse: a review of preclinical studies. Neurosci Biobehav Rev 28:533–546

    Article  PubMed  CAS  Google Scholar 

  • Schramm-Sapyta NL, Walker QD, Caster JM, Levin ED, Kuhn CM (2009) Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models. Psychopharmacol Berl 206:1–21

    Article  CAS  Google Scholar 

  • Shahbazi M, Moffett AM, Williams BF, Frantz KJ (2008) Age- and sex-dependent amphetamine self-administration in rats. Psychopharmacol Berl 196:71–81

    Article  CAS  Google Scholar 

  • Snyder KJ, Katovic NM, Spear LP (1998) Longevity of the expression of behavioral sensitization to cocaine in preweanling rats. Pharmacol Biochem Behav 60:909–914

    Article  PubMed  CAS  Google Scholar 

  • Spear L (2000a) Modeling adolescent development and alcohol use in animals. Alcohol Res Health 24:115–123

    PubMed  CAS  Google Scholar 

  • Spear LP (2000b) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463

    Article  PubMed  CAS  Google Scholar 

  • Spear LP (2009) Heightened stress responsivity and emotional reactivity during pubertal maturation: implications for psychopathology. Dev Psychopathol 21:87–97

    Article  PubMed  Google Scholar 

  • Spencer TJ, Biederman J, Mick E (2007) Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and neurobiology. J Pediatr Psychol 32:631–642

    Article  PubMed  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2010) Results from the 2009 national survey on drug use and health: volume 1. Summary of National Findings. Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4856 Findings, Rockville, MD

  • Valenstein ES, Kakolewski JW, Cox VC (1967) Sex differences in taste preference for glucose and saccharin solutions. Science 156:942–943

    Article  PubMed  CAS  Google Scholar 

  • Vetter CS, Doremus-Fitzwater TL, Spear LP (2007) Time course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions. Alcohol Clin Exp Res 31:1159–1168

    Article  PubMed  CAS  Google Scholar 

  • Wiley MD, Poveromo LB, Antapasis J, Herrera CM, Bolanos Guzman CA (2009) Kappa-opioid system regulates the long-lasting behavioral adaptations induced by early-life exposure to methylphenidate. Neuropsychopharmacology 34:1339–1350

    Article  PubMed  CAS  Google Scholar 

  • Winters KC, Lee CY (2008) Likelihood of develo** an alcohol and cannabis use disorder during youth: association with recent use and age. Drug Alcohol Depend 92:239–247

    Article  PubMed  Google Scholar 

  • Winters KC, Stinchfield RD, Opland E, Weller C, Latimer WW (2000) The effectiveness of the Minnesota Model approach in the treatment of adolescent drug abusers. Addiction 95:601–612

    Article  PubMed  CAS  Google Scholar 

  • Zakharova E, Wade D, Izenwasser S (2009) Sensitivity to cocaine conditioned reward depends on sex and age. Pharmacol Biochem Behav 92:131–134

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This research was supported by the National Institute on Drug Abuse grants, R01 DA 003240-27, R01 DA019942-3, K05 015267-08 (MEC), and F31 DA 023301-02 (JJA). The authors would like to thank Thomas Baron, Luke Gliddon, Nathan Holtz, Seth Johnson, Emily Kidd, Brandon Knight, Brianna Lubben, Paul Regier, Amy Saykao, Matthew Starr, Rachael Turner, Troy Velie, and Jeremy Williams for their technical assistance.

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  1. Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN, 55455, USA

    Justin J. Anker, Natalie E. Zlebnik, Sean F. Navin & Marilyn E. Carroll

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  1. Justin J. Anker
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  2. Natalie E. Zlebnik
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  3. Sean F. Navin
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Correspondence to Justin J. Anker.

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Anker, J.J., Zlebnik, N.E., Navin, S.F. et al. Responding during signaled availability and nonavailability of iv cocaine and food in rats: age and sex differences. Psychopharmacology 215, 785–799 (2011). https://doi.org/10.1007/s00213-011-2181-z

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