Abstract
Adult rats that were gestationally exposed to cocaine and control offspring were examined for their sensitivity to challenge doses of cocaine. Offspring were derived from Sprague-Dawley dams that had received subcutaneous injections of 40 mg/kg per 3 cc cocaine hydrochloride daily on gestational days 8–20, pair-fed dams that were injected with saline, and nontreated control dams. In order to investigate the sensitivity to challenge doses of cocaine, offspring were assessed in adulthood for locomotor activity, cocaine drug discrimination, and the time course of cocaine in brain tissue following acute cocaine challenge. Adult offspring prenatally exposed to cocaine were observed to exhibit a reduced sensitivity to the discriminative stimulus effects of cocaine as evidenced by a significant shift to the right in the dose-response curve of cocaine discrimination. No prenatal treatment effects were observed in terms of the temporal patterns of cocaine discrimination or with regard to brain levels of cocaine. In addition, baseline locomotor activity and locomotor responses to challenge doses of cocaine were comparable across the prenatal treatment groups. Thus, prenatal cocaine exposure reduced sensitivity of offspring to the discriminative stimulus properties of cocaine without altering either the distribution of cocaine to the brain or the sensitivity of the offspring to the locomotor stimulant effects of cocaine.
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Bozarth MA (1989) Conditioned place preference: a parametric analysis using systemic heroin injections. In: Lieberman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Oxford University Press, New York, NY, pp 241–274
Callahan PM, Piercey MF, Cunningham KA (1992) Effects of the putative dopamine autoreceptor antagonists (+)AJ 76 and (+)UH 232 on the discriminative stimulus properties of cocaine. Psychopharmacology 107:73–77
Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. In: Lieberman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Oxford University Press, New York, NY, pp 264–319
Chasnoff IJ, Griffith DR, Freier C, Murray J (1992) Cocaine/polydrug use in pregnancy: two-year follow-up. Pediatrics 89:284–289
Church MW, Overbeck GW (1990) Prenatal cocaine exposure in Long-Evans rat: II Dose-dependent effects on offspring behavior. Neurotoxicol Teratol 12:335–343
Church MW, Kaufman RA, Keenan JA, Martier SS, Savoy-Moore RT, Ostrea EM, Subramanian MG, Welch RA, Zajac CS (1991) Effects of prenatal cocaine exposure. In: Watson RR (ed) Biochemistry and physiology of substance abuse. CRC Press, Boston, MA, pp 179–204
Colpaert FC, Niemegeers CJE, Janssen PAJ (1978) Discriminative stimulus properties of cocaine andd-amphetamine, and antagonism by haloperidol: a comparative study. Neuropharmacology 17:937–942
Cunningham CL, Niehus DR, Malott DH, Prather LK (1992) Genetic differences in the rewarding and activating effects of morphine and ethanol. Psychopharmacology 107:385–393
Dow-Edwards DL, Freed LA, Fico TA (1990) Structural and function effects of prenatal cocaine exposure in adult rat brain. Dev Brain Res 59:263–268
Eisen LN, Field TM, Bandstra ES, Roberts JP, Morrow C, Larson SK, Steele BM (1991) Perinatal cocaine effects on neonatal stress behavior and performance on the Brazelton scale. Pediatrics 88:477–480
Fantel AG, MacPhail BJ (1982) The teratogenicity of cocaine. Teratology 26:17–19
Finney DJ (1964) Statistical methods in biological assay, 2nd edn, Hafner, New York
Foss JA, Riley EP (1991) Failure of acute cocaine administration to differentially affect acoustic startle and activity in rats prenatally exposed to cocaine. Neurotoxicol Teratol 13:547–551
Giordano M, Moody CA, Zubrycki EM, Dreshfield L, Norman AB, Sanberg PR (1990) Prenatal exposure to cocaine in rats: lack of long-term effects on locomotion and stereotypy. Bull Psychon Soc 28:51–54
Henderson MG, McMillen BA (1990) Effects of prenatal exposure to cocaine or related drugs on rat development and neurological indices. Brain Res Bull 24:207–212
Hewlett PS, Plackett RL (1971) The interpretation of quantal responses in biology. University Press, Baltimore, MD
Heyser CJ, Chen WJ, Miller J, Spear NE, Spear LP (1990) Prenatal cocaine exposure induces deficits in Pavlovian conditioning and sensory preconditioning among infant rat pups. Behav Neurosci 104:955–963
Heyser CJ, Goodwin GA, Moody CA, Spear LP (1992a) Prenatal cocaine exposure attenuates cocaine-induced odor preference in infant rats. Pharmacol Biochem Behav.42:169–173
Heyser CJ, Miller JS, Spear NE, Spear LP (1992b) Prenatal exposure to cocaine disrupts cocaine-induced conditioned place preference in rats. Neurotoxicol Teratol 14:57–64
Heyser CJ, Spear NE, Spear LP (1992c) The effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats. Behav Neurosci 106:841–849
Hoffman DC (1989) The use of place conditioning in studying the neuropharmacology of drug reinforcement. Brain Res Bull 23:373–387
Hutchings DE, Fico TA, Dow-Edwards DL (1989) Prenatal cocaine: maternal toxicity, fetal effects and locomotor activity in rat offspring. Neurotoxicol Teratol 11:65–69
Järbe TUC (1978) Cocaine as a discriminative cue in rats: interactions with neuroleptics and other drugs. Psychopharmacology 59:183–187
Järbe TUC (1987) Drug discrimination learning: cue properties of drugs. In: Greenshaw AJ, Dourish CT (eds) Experimental psychopharmacology. Humana Press, Clifton, NJ, pp 433–479
Kato R (1974) Sex-related differences in drug metabolism. Drug Metab Rev 3:1–32
Katz JL, Griffiths JW, Sharpe LG, De Souza EB, Witkin JM (1993) Cocaine tolerance and cross-tolerance. J Pharmacol Exp Ther 264:185–192
Kirk RE (1982) Experimental design: procedures for the behavioral sciences, 2nd edn. Brooks/Cole, Belmont, CA
Mahalik MP, Gautieri RF, Mann DE (1980) Teratogenic potential of cocaine hydrochloride in CF-1 mice. J Pharm Sci 69:703–706
Mahalik MP, Gautieri RF, Mann DE (1984) Mechanisms of cocaine-induced teratogenesis. Res Commun Subst Abuse 5:279–302
McKenna ML, Ho BT (1980) The role of dopamine in the discriminative stimulus properties of cocaine. Neuropharmacology 19:297–303
Meyer JS, Sherlock JD, MacDonald NR (1992) Effects of prenatal cocaine on behavioral responses to a cocaine challenge on postnatal day 11. Neurotoxicol Teratol 14:183–189
Middaugh LD, Ayers L (1988) Effects of ethanol on mature offspring of mice given ethanol during pregnancy. Alcohol Clin Exp Res 12:388–393
Minabe Y, Ashby CR Jr, Heyser C, Spear LP, Wang RY (1992) The effects of prenatal cocaine exposure on spontaneously active midbrain dopamine neurons in postnatal male rats: an electrophysiological study. Brain Res 586:152–156
Moody CA, Frambes NA, Spear LP (1992) Psychopharmacological responsiveness to the dopamine agonist quinpirole in normal weanlings and in weanling offspring exposed gestationally to cocaine. Psychopharmacology 108:256–262
Overton DA (1979) Drug discrimination training with progressively lowered doses. Science 205:720–721
Overton DA (1987) Applications of the drug discrimination method for the study of drug abuse. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, New York, NY, pp 291–340
Peris J, Coleman-Hardee M, Millard WJ (1992) Cocaine in utero enhances the behavioral responses to cocaine in adult rats. Pharmacol Biochem Behav 42:509–515
Phillips TJ, Crabbe JC (1991) Behavioral studies of genetic differences in alcohol action. In: Crabbe JC, Harris RA (eds) The genetic basis of alcohol and drug actions. Plenum Press, New York, NY, pp 25–104
Plessinger MA, Woods JR Jr (1991) The cardiovascular effects of cocaine use in pregnancy. Reprod Toxicol 5:99–113
Riley EP, Foss JA (1991) Exploratory behavior and locomotor activity: a failure to find effects in animals prenatally exposed to cocaine. Neurotoxicol Teratol 13:553–558
Rowbotham MC, Lowenstein DH (1990) Neurological consequences of cocaine use. Annu Rev Med 41:417–422
Scalzo FM, Ali SF, Frambes NA, Spear LP (1990) Weanling rats exposed prenatally to cocaine exhibit an increase in striatal D2 binding associated with an increase in ligand affinity. Pharmacol Biochem Behav 37:371–373
Schechter MD (1989) Temporal parameters of cathinone, amphetamine and cocaine. Pharmacol Biochem Behav 34:289–292
Seidler FJ, Slotkin TA (1992) Fetal cocaine exposure causes persistent noradrenergic hyperactivity in rat brain regions: Effects on neurotransmitter turnover and receptors. J Pharmacol Exp Ther 263:413–421
Shah NS, May DA, Yates JD (1980) Disposition of levo-[3h]cocaine in pregnant and nonpregnant mice. Toxicol Appl Pharmacol 53:279–284
Slutsker LT (1992) Risks associated with cocaine use during pregnancy. Obstet Gynecol 79:778–789
Sobrian SK, Burton LE, Robinson NL, Ashe WK, James H, Stokes DL, Turner LM (1990) Neurobehavioral and immunological effects of prenatal cocaine exposure in rat. Pharmacol Biochem Behav 35:617–629
Spear LP, Heyser CJ (1992) Cocaine and the developing nervous system: laboratory findings. In: Zagon IS, Slotkin TA (eds) Maternal substance abuse and the developing nervous system. Academic Press, Orlando, FL, pp 155–175
Spear LP, Heyser CJ (1993) Is use of a cellulose-diluted diet a viable alternative to pair-feeding? Neurotoxicol Teratol 15:85–89
Spear LP, Frambes NA, Kirstein CL (1989a) Fetal and maternal brain and plasma levels of cocaine and benzoylecgonine following chronic subcutaneous administration of cocaine during gestation in rats. Psychopharmacology 97:427–431
Spear LP, Kirstein CL, Bell J, Yoottanasumpun V, Greenbaum R, O'Shea J, Hoffmann H, Spear NE (1989b) Effects of prenatal cocaine exposure on behavior during the early postnatal period. Neurotoxicol Teratol 11:57–63
Spear LP, Kirstein CL, Frambes NA (1989c) Cocaine effects on the developing central nervous system: behavioral, psychopharmacological, and neurochemical studies. Ann NY Acad Sci 526:290–307
Van der Kooy D (1989) Place conditioning: A simple and effective method for assessing the motivational properties of drugs. In: Lieberman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Oxford University Press, New York, NY, pp 229–240
Van Haaren F, van Hest A, Heinsbroek RPW (1990) Behavioral differences between male and female rats: effects of gonadal hormones on learning and memory. Neurosci Biobehav Rev 14:23–33
Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263
Witkin JM, Nichols DE, Terry P, Katz JL (1991) Behavioral effects of selective dopaminergic compounds in rats discriminating cocaine injections. J Pharmacol Exp Ther 257:706–713
Woolverton WL, Cervo L (1986) Effects of central dopamine depletion on thed-amphetamine discriminative stimulus in rats. Psychopharmacology 88:196–200
Wood DM, Emmett-Oglesby MW (1988) Substitution and cross-tolerance profiles of anorectic drugs in rats trained to detect the discriminative stimulus properties of cocaine. Psychopharmacology 95:364–368
Zenick H, Goldsmith M (1981) Drug discrimination learning in lead-exposed rats. Science 212:569–571
Zuckerman B, Bresnahan K (1991) Developmental and behavioral consequences of prenatal drug and alcohol exposure. Pediatric Clin North Am 38:1287–1306
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Heyser, C.J., Rajachandran, L., Spear, N.E. et al. Responsiveness to cocaine challenge in adult rats following prenatal exposure to cocaine. Psychopharmacology 116, 45–55 (1994). https://doi.org/10.1007/BF02244870
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DOI: https://doi.org/10.1007/BF02244870