Abstract
Rationale
Previously, we demonstrated that neonatal isolation increases acquisition of cocaine self-administration in adult male rats.
Objective
Now we examine whether neonatal isolation enhances maintenance and cocaine-induced reinstatement of extinguished self-administration behavior. To test the specificity of the effect, a separate study examined maintenance of food responding.
Methods
Litters were subjected to neonatal isolation (individual isolation; 1 h/day; postnatal days 2–9) or were non-handled. In experiment 1, adult male rats trained to self-administer cocaine (0.5 mg/kg per infusion; fixed-ratio 3 or FR3) were tested under fixed and progressive ratio (PR) schedules with different cocaine doses (0.125–1.0 mg/kg per infusion). After cocaine self-administration was extinguished, cocaine (0.5 or 2 mg/kg)-induced reinstatement of responding was assessed. In experiment 2, responding for food under an FR15 and two PR schedules were assessed in separate groups of neonatally isolated and non-handled male rats.
Results
Neonatally isolated rats responded for low cocaine doses at higher rates and infused more cocaine relative to non-handled rats under both FR and PR schedules. However, there are no group differences in cocaine-induced reinstatement or in responding for food under the PR schedules. However, neonatally isolated rats lever pressed for food at lower rates under the FR schedule.
Conclusions
Together with our previous studies, the results of the present study suggest that the early life stress of neonatal isolation enhances cocaine-taking (acquisition and maintenance) at lower doses but does not alter drug-induced cocaine-seeking (reinstatement) behavior.
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References
Bardo MT, Donohew RL, Harrington NG (1996) Psychobiology of novelty seeking and drug seeking behavior. Behav Brain Res 77:23–43
Bergman J, Madras BK, Johnson SE, Spealman RD (1989) Effects of cocaine and related drugs in nonhuman primates III: self-administration by squirrel monkeys. J Pharmacol Exp Ther 251:150–155
Deroche V, Marinelli M, LeMoal M, Piazza PV (1997) Glucocorticoids and behavioral effects of psychostimulants. II: cocaine intravenous self-administration and reinstatement depend on glucocorticoid levels. J Pharmacol Exp Ther 281:1401–1407
Deutch AY, Roth RH (1990) The determinants of stress-induced activation of the prefrontal cortical dopamine system. Prog Brain Res 85:357–393
DeVries T, Schoffelmeer ANM, Binnekade R, Mulder AH, Vanderschuren LJMJ (1998) MK-801 reinstates drug-seeking behaviour in cocaine-trained rats. Neuroreport 9:637–640
deWit H, Stewart J (1981) Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75:134–143
Dinwiddie SH, Reich T, Cloninger CR (1992) Prediction of intravenous drug use. Compr Psychiatry 33:173–179
Dunn AJ, Berridge CW (1990) Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses? Brain Res Rev 15:71–100
Goeders NE, Guerin GF (1996) Role of corticosterone in intravenous cocaine self-administration in rats. Neuroendocrinology 64:337–348
Gordon HW (2002) Early environmental stress and biological vulnerability to drug abuse. Psychoneuroendocrinology 27:115–126
Gutierres SE, Molof M, Ungerleider S (1994) Relationship of “risk” factors to teen substance use: a comparison of abstainers, infrequent users, and frequent users. Int J Addict 12:1047–1056
Haile CN, Kosten TA (2001) Differential effects of D1- and D2-like compounds on cocaine self-administration in Lewis and Fischer 344 inbred rats. J Pharmacol Exp Ther 299:509–518
Hall FS, Wilkinson LS, Humby T, Robbins TW (1999) Maternal deprivation of neonatal rats produces enduring changes in dopamine function. Synapse 32:37–43
Haney M, Maccari S, LeMoal M, Simon H, Piazza PV (1995) Social stress increases the acquisition of cocaine self-administration in male and female rats. Brain Res 698:46–52
Hodos W (1961) Progessive ratio as a measure of reward. Science 134:943–944
Katz JL (1989) Drugs as reinforcers: pharmacological and behavioral factors. In: Liebman J, Coopers S (eds) The neuropharmacological basis of reward. Oxford, New York, pp 164–213
Katz JL, Higgins ST (2003) The validity of the reinstatement model of craving and relapse to drug use. Psychopharmacology 168:21–30
Kehoe P, Shoemaker WJ, Triano L, Hoffman J, Arons C (1996) Repeated isolation in the neonatal rat produces alterations in behavior and ventral striatal dopamine release in the juvenile following amphetamine challenge. Behav Neurosci 110:1434–1444
Kehoe P, Shoemaker WJ, Arons C, Triano L, Suresh G (1998) Repeated isolation stress in the neonatal rat: relation to brain dopamine systems in the 10-day-old rat. Behav Neurosci 112:1466–1474
Kendler KS, Bulik CM, Silberg J, Hettema JM, Myers J, Prescott CA (2000) Childhood sexual abuse and adult psychiatric and substance use disorders in women. Arch Gen Psychiatry 57:953–959
Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723
Kosten TA, Miserendino MJD, Haile CN, DeCaprio JL, Jatlow PI, Nestler EJ (1997) Acquisition and maintenance of intravenous cocaine self-administration in Lewis and Fischer inbred rat strains. Brain Res 778:418–429
Kosten TA, Miserendino MJD, Kehoe P (2000) Enhanced acquisition of cocaine self-administration in adult rats with neonatal isolation stress experience. Brain Res 875:20–31
Kosten TA, Zhang XY, Kehoe P (2003) Chronic neonatal isolation stress enhances cocaine-induced increases in ventral striatal dopamine levels in rat pups. Brain Res Dev Brain Res 141:109–116
Kosten TA, Sanchez H, Zhang XY, Kehoe P (2004) Neonatal isolation enhances acquisition of cocaine self-administration and food responding in female rats. Behav Brain Res 151:137–149
Lehmann J, Feldon J (2000) Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing? Rev Neurosci 11:383–408
Lu L, Shepard JD, Hall FS, Shaham Y (2003) Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review. Neurosci Biobehav Rev 27:457–491
Markou A, Weiss F, Gold LH, Schulteis SBCG, Koob GF (1993) Animal models of drug craving. Psychopharmacology 112:163–182
Matthews K, Robbins TW, Everitt BJ, Caine SB (1999) Repeated neonatal maternal separation alters intravenous cocaine self-administration in adult rats. Psychopharmacology 141:123–134
McCormick CM, Kehoe P, Kovacs S (1998) Corticosterone release in response to repeated, short episodes of neonatal isolation: evidence of sensitization. Int J Dev Neurosci 16:175–185
McCormick CM, Kehoe P, Mallinson K, Cecchi L, Frye CA (2002) Neonatal isolation alters stress hormone and mesolimbic dopamine release in juvenile rats. Pharmacol Biochem Behav 73:77–85
Meaney MJ, Diorio R, Francis D, Widdowson J, LaPlante P, Caldji C, Sharm V, Seckl JR, Plotsky PM (1996) Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev Neurosci 18:49–72
Miczek KA, Mutschler NH (1996) Activational effects of social stress on IV cocaine self-administration in rats. Psychopharmacology 128:256–264
Papaioannou A, Dafni U, Alikaridis F, Bolaris S, Stylianopoulou F (2002) Effects of neonatal handling on basal and stress-induced monoamine levels in the male and female rat brain. Neuroscience 114:195–206
Pettit HO, Justice JB (1989) Dopamine in the nucleus accumbens during cocaine self-administration as studied by in vivo microdialysis. Pharmacol Biochem Behav 34:899–904
Piazza PV, LeMoal M (1998) The role of stress in drug self-administration. Trends Pharmacol Sci 19:67–74
Piazza PV, Deminiere J-M, LeMoal M, Simon H (1990) Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration. Brain Res 514:22–26
Piazza PV, Maccari S, Deminiere JM, LeMoal M, Mormede P, Simon H (1991) Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc Natl Acad Sci 88:2088–2092
Plotsky PM, Meaney MJ (1993) Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Mol Brain Res 18:195–200
Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223
Rivier CL, Plotsky PM (1986) Mediation by corticotropin releasing factor (CRF) of adrenohypophysial hormone secretion. Annu Rev Physiol 48:475–494
Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive sensitization theory of addiction. Brain Res Rev 18:247–291
Rodefer JS, Carroll ME (1996) Progressive ratio and behavioral economic evaluation of the reinforcing efficacy of orally delivered phencyclidine and ethanol in monkeys: effects of feeding conditions. Psychopharmacology 128:265–273
Salamone JD (1992) Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes. Psychopharmacology 107:160–174
Shaham Y, Stewart J (1994) Exposure to mild stress enhances the reinforcing efficacy of intravenous heroin in rats. Psychopharmacology 114:523–527
Shalev U, Kafkafi N (2002) Repeated maternal separation does not alter sucrose-reinforced and open-field behaviors. Pharmacol Biochem Behav 73:115–122
Shalev U, Grimm JW, Shaham Y (2002) Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42
Spealman RD, Bergman J, Madras BK, Kamien JB, Melia KF (1992) Role of D1 and D2 dopamine receptors in the behavioral effects of cocaine. Neurochem Int 20(Suppl):147S–152S
Stewart J, deWit H (1987) Reinstatement of drug-taking behavior as a method of assessing incentive motivational properties of drugs. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 211–227
Tidey JW, Miczek KA (1997) Acquisition of cocaine self-administration after social stress: role of accumbens dopamine. Psychopharmacology 130:203–212
Winer BJ (1962). Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York
Wise RA, Rompre PP (1989) Brain dopamine and reward. In: Rosenzweig MR, Porter LW (eds) Annual review of psychology. Annual Reviews Inc, Palo Alto, pp 191–225
Acknowledgements
This research was supported by the Patrick and Catherine Weldon Donaghue Foundation (DF # 00-202) and by the Yale IWHR Scholar Program on Women and Drug Abuse (1K12DA14038). The authors gratefully acknowledge the technical assistance provided by Tashi King, Joanne Lee, and Diane Lendroth.
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Zhang, X.Y., Sanchez, H., Kehoe, P. et al. Neonatal isolation enhances maintenance but not reinstatement of cocaine self-administration in adult male rats. Psychopharmacology 177, 391–399 (2005). https://doi.org/10.1007/s00213-004-1963-y
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DOI: https://doi.org/10.1007/s00213-004-1963-y