Abstract
Rationale
Rats selectively bred for high saccharin (HiS) intake consume more alcohol and acquire intravenous (IV) cocaine self-administration more rapidly than their low saccharin (LoS) consuming counterparts.
Objectives
The purpose of the present study was to determine whether HiS and LoS rats also differ in the escalation, maintenance, and reinstatement of IV cocaine self-administration.
Methods
LoS and HiS female rats were allowed to self-administer cocaine [0.4 mg/kg; fixed ratio (FR) 1] under short (ShA, 2 h per day) or long (LgA, 12 h per day) access conditions for 21 days. Session lengths were subsequently equated (2 h) and (1) FR1-maintained cocaine (0.4 mg/kg) self-administration, (2) progressive ratio (PR)-maintained cocaine (0.2–1.6 mg/kg) self-administration, and (3) saline-induced and cocaine (10 mg/kg, IP)-induced reinstatement of drug-seeking behavior were examined.
Results
HiS LgA rats escalated their cocaine intake more rapidly and self-administered more cocaine (mg/kg) than LoS LgA rats; however, there was no LoS versus HiS phenotype difference in the number of infusions self-administered by Day 21. Post-escalation cocaine self-administration under an FR1 schedule did not differ as a function of phenotype (LoS versus HiS) or access condition (ShA versus LgA); however, LoS rats responded more for cocaine under the PR schedule than HiS rats, and they showed a greater reinstatement of cocaine-seeking behavior than HiS rats. In contrast, ShA versus LgA did not affect PR or reinstatement performance in the LoS and HiS groups.
Conclusions
These results suggest that LoS and HiS rats have distinct drug-seeking and drug-taking profiles that differ as a function of the experimental phase and access condition. The LoS and HiS rats differ along a wide range of behavioral dimensions and represent an important model to study the interactions of feeding, emotionality, and other factors related to vulnerability to drug abuse.
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References
Ahmed SH, Koob GF (1998) Transition from moderate to excessive drug intake: change in hedonic set point. Science 282:298–300
Ahmed SH, Koob GF (1999) Long-lasting increase in the set point for cocaine self-administration after escalation in rats. Psychopharmacology 146:303–312
Badia-Elder N, Kiefer SW, Dess NK (1996) Taste reactivity in rats selectively bred for high versus. low saccharin consumption. Physiol Behav 59:749–755
Belknap JK, Crabbe JC, Young ER (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112:503–510
Carroll ME (1993) The economic context of drug and non-drug reinforcers affects acquisition and maintenance of drug-reinforced behavior and withdrawal effects. Drug Alcohol Depend 33:201–210
Carroll ME (1999) Interactions between food and addiction. In: Niesink RJM, Hoefakker RE, Westera W, Jaspers RMA, Kornet LMW, Boobis S (eds) Neurobehavioral toxicology and addiction: food, drugs and environment. CRC, Boca Raton, pp 286–311
Carroll ME, Campbell UC (2000) A behavioral economic analysis of the reinforcing effects of drugs: transition states of addiction. In: Bickel WK, Vuchinich RE (eds) Reframing health behavior change with behavioral economics. Lawrence Erlbaum, Mahwah, pp 63–87
Carroll ME, Comer SD (1996) Animal models of relapse. Exp Clin Psychopharmacol 4:11–18
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. Psychopharmacology 161:304–313
Carroll ME, Lynch WC, Roth ME, Morgan AD, Cosgrove KP (2004) Sex and estrogen influence drug abuse. Trends Pharmacol Sci (in press)
Cools AR, Gingras MA (1998) Nijmegen high and low responders to novelty: a new tool in the search after the neurobiology of drug abuse liability. Pharmacol Biochem Behav 60:151–159
Crabbe JC (2002) Genetic contributions to addiction. Annu Rev Psychol 53:435–462
Dellu F, Piazza PV, Mayo W, Le Moal M, Simon H (1996) Novelty-seeking in rats—biobehavioral characteristics and possible relationship with the sensation-seeking trait in man. Neuropsychobiology 34:136–145
Dess NK, Minor TR (1996) Taste and emotionality in rats selectively bred for high versus low saccharin intake. Anim Learn Behav 24:105–115
Dess NK, Badia-Elder NE, Thiele TE, Kiefer SW, Blizard DA (1998) Ethanol consumption in rats selectively bred for differential saccharin intake. Alcohol 16:275–278
Dess NK, Arnal J, Chapman CD, Siebel S, VanderWeele DA (2002) Exploring adaptations to famine: rats selectively bred for differential intake of saccharin differ on deprivation-induced hyperactivity and emotionality. Int J Comp Psychol 13:34–52
Fitch TE, Roberts DC (1993) The effects of dose and access restrictions on the periodicity of cocaine self-administration in the rat. Drug Alcohol Depend 33:119–128
Gahtan E, Labounty LP, Wyvell C, Carroll ME (1996) The relationships among saccharin consumption, oral ethanol, and IV cocaine self-administration. Pharmacol Biochem Behav 53:919–925
Goeders NE (2002) Stress and cocaine addiction. J Pharmacol Exp Ther 301:785–789
Gosnell BA, Krahn DD (1992) The relationship between saccharin and alcohol intake in rats. Alcohol 9:203–206
Gosnell BA, Krahn DD (1998) Taste and diet preferences as predictors of drug self-administration. NIDA Res Monogr 169:154–175
Haile CN, Kosten TA (2000) Differential effects of D1-and D2-like compounds on the discriminative stimulus and reinforcing effects of cocaine in Lewis and Fischer rats. College on problems of drug dependence. Drug and alcohol dependence. Elsevier, San Juan
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
Homberg JR, van den Akker M, Raaso HS, Wardeh G, Binnekade R, Schoffelmeer AN, de Vries TJ (2002) Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala. Eur J Neurosci 15:1542–1550
Hooks MS, Jones GH, Smith AD, Neill DB, Justice JB Jr (1991a) Individual differences in locomotor activity and sensitization. Pharmacol Biochem Behav 38:467–470
Hooks MS, Jones GH, Smith AD, Neill DB, Justice JB Jr (1991b) Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine. Synapse 9:121–128
Johanson CE, Balster RL, Bonese K (1976) Self-administration of psychomotor stimulant drugs: the effects of unlimited access. Pharmacol Biochem Behav 4:45–51
Kampov-Polevoy AB, Overstreet DH, Rezvani AH, Janowsky DS (1995) Suppression of ethanol intake in alcohol-preferring rats by prior voluntary saccharin consumption. Pharmacol Biochem Behav 52:59–64
Kampov-Polevoy AB, Garbutt JC, Janowsky DS (1999) Association between preference for sweets and excessive alcohol intake: a review of animal and human studies. Alcohol Alcohol 34:386–395
Koros E, Piasecki J, Kostowski W, Bienkowski P (1998) Saccharin drinking rather than open field behaviour predicts initial ethanol acceptance in Wistar rats. Alcohol Alcohol 33:131–140
Kosten TA, Miserendino MJ, 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
Levine AS, Kotz CM, Gosnell BA (2003a) Sugars and fats: the neurobiology of preference. J Nutr 133:831S–834S
Levine AS, Kotz CM, Gosnell BA (2003b) Sugars: hedonic aspects, neuroregulation, and energy balance. Am J Clin Nutr 78:834S–842S
Li TK, Lumeng L, Doolittle DP (1993) Selective breeding for alcohol preference and associated responses. Behav Genet 23:163–170
Lynch WJ, Roth ME, Carroll ME (2002) Biological basis of sex differences in drug abuse: preclinical and clinical studies. Psychopharmacology 164:121–137
Mantsch JR, Ho A, Schlussman SD, Kreek MJ (2001) Predictable individual differences in the initiation of cocaine self-administration by rats under extended-access conditions are dose-dependent. Psychopharmacology 157:31–39
McClearn GE, Rodgers DA (1959) Differences in alcohol preference among inbred strains of mice. Q J Stud Alcohol 20:691–695
Morgan AD, Campbell UC, Fons RD, Carroll ME (2002) Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats. Pharmacol Biochem Behav 72:873–880
National Research Council (2003) Guide for the care and use of mammals in neuroscience and behavioral research. The National Academies, Washington
Nestler EJ (2000) Genes and addiction. Nat Genet 26:277–281
Piazza PV, Deminiere JM, Le Moal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–1513
Piazza PV, Deminiere JM, Maccari S, Mormede P, Le Moal M, Simon H (1990) Individual reactivity to novelty predicts probability of amphetamine self-administration. Behav Pharmacol 1:339–345
Piazza PV, Deroche V, Rouge-Pont F, Le Moal M (1998) Behavioral and biological factors associated with individual vulnerability to psychostimulant abuse. NIDA Res Monogr 169:105–133
Ramos A, Mormede P (1998) Stress and emotionality: a multidimensional and genetic approach. Neurosci Biobehav Rev 22:33–57
Ranaldi R, Bauco P, McCormick S, Cools AR, Wise RA (2001) Equal sensitivity to cocaine reward in addiction-prone and addiction-resistant rat genotypes. Behav Pharmacol 12:527–534
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
Roth ME, Carroll ME (2004) Sex differences in the escalation of IV cocaine intake following long- or short-access to cocaine for self-administration. Pharmacol Biochem Behav 78:199–207
Rowlett JK (2000) A labor-supply analysis of cocaine self-administration under progressive-ratio schedules: antecedents, methodologies, and perspectives. Psychopharmacology 153:1–16
Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20
Sinclair JD, Kampov-Polevoy A, Stewart R, Li TK (1992) Taste preferences in rat lines selected for low and high alcohol consumption. Alcohol 9:155–160
Stafford D, LeSage MG, Glowa JR (1998) Progressive-ratio schedules of drug delivery in the analysis of drug self-administration: a review. Psychopharmacology 139:169–184
VanderWeele DA, Dess NK, Castonguay TW (2002) Ingestional responses to metabolic challenges in rats selectively bred for high and low saccharin intake. Physiol Behav 75:97–104
Vries TJ de, Schoffelmeer AN, Binnekade R, Mulder AH, Vanderschuren LJ (1998) Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization. Eur J Neurosci 10:3565–3571
Acknowledgements
The authors would like to thank Jennifer L. Perry and Erin B. Larson for careful reading of this manuscript, and Annemarie K. Loth, Justin Anker, and Marissa M. Anderson for their technical assistance. This work was supported by NIH grants T32 DA07097 (A.D.M.), RO1 DA03240, and K05 DA15267 (M.E.C.).
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-005-2245-z
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Morgan, A.D., Dess, N.K. & Carroll, M.E. Escalation of intravenous cocaine self-administration, progressive-ratio performance, and reinstatement in rats selectively bred for high (HiS) and low (LoS) saccharin intake. Psychopharmacology 178, 41–51 (2005). https://doi.org/10.1007/s00213-004-1979-3
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DOI: https://doi.org/10.1007/s00213-004-1979-3