Skip to main content
SpringerLink
Log in

Preliminary evidence for methamphetamine-induced behavioral and ocular effects in rat offspring following exposure during early organogenesis

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Gravid Sprague-Dawley CD (VAF) rats received 50 mg/kg (d,l)-methamphetamine (MA) HCl (expressed as free base,N=15) or distilled water (N=6) by SC injection × 2/day in a 3 ml/kg volume on embryonic (E) days 7–12. Control rats were pair-fed to MA-exposed dams on days E7–18. No control dams failed to deliver; however, of 15 MA-exposed dams 4 did not deliver (2 died and 2 had completely resorbed litters). One additional MA litter had all the offspring die shortly after birth. There was no difference between groups on offspring postnatal (P) body weight. The offspring exposed prenatally to MA had significantly lower olfactory orientation scores (P9, 11, 13) to their home cage scent. In a test of early activity (P10, 12, 14) the MA-exposed progeny were marginally less active than controls. MA-exposed offspring exhibited hyperreactivity and marginally shortened response latency on a test of acoustic startle (P27). Motor activity showed no differential response in MA treated or control offspring to MA (P63) or fluoxetine challenge (P70). However, the MA offspring were more active than controls with respect to central and side activity during the second week of testing. No group differences were found for performance in a straight swimming channel or on the number of errors committed or latency to escape in a complex (Cincinnati) water maze (P84). Prenatal exposure to MA also induced eye defects (i.e., anophthalmia, microphthalmia and folded retina) in 16.7% of the progeny. However, MA did not effect hippocampal or neostriatal monoamine levels when measured on P28. These data support the hypothesis that MA is behaviorally and ocularly teratogenic to the developing rat and results in functional deficits when compared to offspring of pair-fed controls.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams J, Buelke-Sam J, Kimmel CA, LaBorde JB (1982) Behavioral alterations in rats prenatally exposed to low doses ofd-amphetamine. Neurobehav Toxicol Teratol 4:63–70

    PubMed  Google Scholar 

  • Ando K, Johanson CE, Seiden LS, Schuster CR (1984) Sensitivity changes to dopamine agents in fine motor control of rhesus monkeys after repeated methamphetamine administration. Pharmacol Biochem Behav 22:737–743

    Article  Google Scholar 

  • Battaglia G, Cabrera TM, Tung F, Levy AD, Rittenhouse PA, Li Q, Yracheta J, Kunimoto K, Handa RJ, Van de Kar LD (1991) Long term functional alterations in serotonergic systems following in utero exposure to methamphetamine. Soc Neurosci Abstr 17:889

    Google Scholar 

  • Bell RW, Drucker RR, Woodruff AB (1965) The effects of prenatal injections of adrenalin chloride andd-amphetamine sulfate on subsequent emotionality and ulcer proneness of offspring. Psychon Sci 2:269–270

    Google Scholar 

  • Biel WC (1940) Early age differences in the maze performance of the albino rat. J Genet Psychol 56:439–453

    Google Scholar 

  • Bittner SE, Wagner GC, Aigner TG, Seiden LS (1981) Effects of a high dose treatment of methamphetamine on caudate dopamine and anorexia in rats. Pharmacol Biochem Behav 14:481–486

    Article  PubMed  Google Scholar 

  • Buelke-Sam J, Kimmel CA, Adams J, Miller DR, Nelson CJ (1982) Behavioral assessment of rats treated prenatally with low doses ofd-amphetamine: II. Activity and pharmacological challenge testing. Teratology 25:30A/31A

  • Burchfield DJ, Lucas VW, Abrams RM, Miller RL, DeVane CL (1991) Disposition and pharmacodynamics of methamphetamine in pregnant sheep. JAMA 265[15]:1968–1973

    Article  PubMed  Google Scholar 

  • Cabrera TM, Cross MK, George M, Petrovic L, Clancy J Jr, Handa RJ, Lorens SA (1990) In utero exposure to methamphetamine (Meth): effects on neural, endocrine and immune functions in male rats. Soc Neurosci Abstr 16:33

    Google Scholar 

  • Caldecott-Hazard S, Clark R, Derrig K, McCunniff K (1990) Effects of in utero methamphetamine on rat offspring. Soc Neurosci Abstr 16:586

    Google Scholar 

  • Cho AK (1990) Ice: A new dosage form of an old drug. Science 249:631–634

    Google Scholar 

  • Clark CV, Gorman D, Vernadakis A (1970) Effects of prenatal administration of psychotropic drugs on behavior of developing rats. Dev Psychobiol 3[4]:225–235

    Article  PubMed  Google Scholar 

  • Commins DE, Axt KJ, Vosmer G, Seiden LS (1987) 5,6-Dihydroxytryptamine, a serotonergic neurotoxin, is formed endogenously in the rat brain. Brain Res 403:7–14

    Article  PubMed  Google Scholar 

  • Courtney KD, Valerio DA (1968) Teratology in theMacaca mulatta. Teratology 1:163–172

    Article  PubMed  Google Scholar 

  • Derlet RW, Heischober B (1990) Methamphetamine: Stimulant of the 1990s? West J Med 153[6]:625–628

    PubMed  Google Scholar 

  • DeVito MJ, Wagner GC (1989) Functional consequences following methamphetamine-induced neuronal damage. Psychopharmacology 97:432–435

    Article  PubMed  Google Scholar 

  • Dixon SD (1989) Effects of transplacental exposure to cocaine and methamphetamine on the neonate. West J Med 150:436–442

    PubMed  Google Scholar 

  • Dixon SD, Bejar R (1989) Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: incidence and clinical correlates. J Pediatr 115[5]:770–778

    PubMed  Google Scholar 

  • Dykens JA, Stern A, Trenkner E (1987) Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury. J Neurochem 49:1222–1228

    PubMed  Google Scholar 

  • Ellison, G, Eison, MS, Huberman, HS, Daniel, F (1978) Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Science 201:276–278

    PubMed  Google Scholar 

  • Fischman MW, Schuster CR (1977) Long-term behavioral changes in the rhesus monkey after multiple daily injections ofd-methamphetamine. J Pharmacol Exp Ther 201:593–605

    PubMed  Google Scholar 

  • Hitzemann BA, Hitzemann RJ, Brase DA, Loh HH (1976) Infuence of prenatald-amphetamine administration on development and behavior of rats. Life Sci 18:605–612

    Article  PubMed  Google Scholar 

  • Holson R, Adams J, Buelke-Sam J, Gough B, Kimmel CA (1985)d-Amphetamine as a behavioral teratogen: effects depend on dose, sex, age and task. Neurobehav Toxicol Teratol 7:753–758

    PubMed  Google Scholar 

  • Kasirsky G, Tansy MF (1971) Teratogenic effects of methamphetamine in mice and rabbits. Teratology 4:131–134

    Article  Google Scholar 

  • Little BB, Snell LM, Gilstrap LC (1988) Methamphetamine abuse during pregnancy: outcome and fetal effects. Obstet Gynecol 72[4]:541–544

    PubMed  Google Scholar 

  • Lorens SA, Hata N, Handa RJ, Van de Kar LD, Guschwan M, Goral J, Lee JM, Hamilton ME, Bethea CL, Clancy J (1990) Neurochemical endocrine and immunological responses to stress in young and old Fischer 344 male rats. Neurobiol Aging 11:139–150

    Article  PubMed  Google Scholar 

  • Lorez H (1981) Fluorescence histochemistry indicates damage of striatal dopamine nerve terminals in rats after multiple doses of methamphetamine. Life Sci 28:911–916

    Article  PubMed  Google Scholar 

  • Lucot JB, Wagner GC, Schuster CR, Seiden LS (1980) Effects of dopaminergic agents on the locomotor activity after high doses of methamphetamine. Pharmacol Biochem Behav 13:409–413

    Article  PubMed  Google Scholar 

  • Lucot JB, Wagner GC, Schuster CR, Seiden LS (1982) Decreased sensitivity of rat pups to long-lasting dopamine and serotonin depletions produced by methylamphetamine. Brain Res 247:181–183

    Article  PubMed  Google Scholar 

  • Martin JC (1975) Effects on offspring of chronic maternal methamphetamine exposure. Dev Psychobiol 8:397–404

    Article  PubMed  Google Scholar 

  • Martin JC, Martin DC (1981) Voluntary activity in the aging rat as a function of maternal drug exposure. Neurobehav Toxicol Teratol 3:261–264

    PubMed  Google Scholar 

  • Martin JC, Martin DC, Radow B, Sigman G (1976) Growth, development and activity in rat offspring following maternal drug exposure. Exp Aging Res 2:235–251

    PubMed  Google Scholar 

  • Middaugh LD (1989) Prenatal amphetamine effects on behavior: possible mediation by brain monoamines. Ann NY Acad Sci 562:308–318

    PubMed  Google Scholar 

  • Middaugh LD, Blackwell LA, Santos CA, Zemp JW (1974) Effects ofd-amphetamine sulfate given to pregnant mice on activity and on catecholamines in the brains of offspring. Dev Psychobiol 7[5]:429–438

    Article  PubMed  Google Scholar 

  • Monder H (1981) Effects of prenatal amphetamine exposure on the development of behavior in rats. Psychopharmacology 75:75–78

    Article  PubMed  Google Scholar 

  • Nasello AG, Ramirez OA (1978) Open field and Lashley III maze behaviour of the offspring of amphetamine-treated rats. Psychopharmacology 58:171–173

    Article  PubMed  Google Scholar 

  • Nasello AG, Astrada CA, Ramirez OA (1974) Effects on the acquisition of conditioned avoidance responses and seizure threshold in the offspring of amphetamine treated gravid rats. Psychopharmacologia 40:25–31

    Article  PubMed  Google Scholar 

  • Nwanze, E, Jonsson, G (1981) Amphetamine neurotoxicity on dopamine nerve terminals in the caudate nucleus of mice. Neurosci Lett 26:163–168

    Article  PubMed  Google Scholar 

  • Oro AS, Dixon SD (1987) Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates. J Pediatr 111[4]:571–578

    PubMed  Google Scholar 

  • Ricaurte GA, Schuster CR, Seiden LS (1980) Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: a regional study. Brain Res 193:153–163

    Article  PubMed  Google Scholar 

  • Ricaurte GA, Guillery RW, Seiden LS, Schuster CR, Moore RY (1982) Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain. Brain Res 235:93–103

    Article  PubMed  Google Scholar 

  • Ricaurte GA, Seiden LS, Schuster CR (1983) Increased dopamine metabolism in the rat neostriatum after toxic doses ofd-methamphetamine. Neuropharmacology 22:1381–1388

    Google Scholar 

  • Ricaurte GA, Seiden LS, Schuster CR (1984) Further evidence that amphetamines produce long-lasting dopamine neurochemical deficits by destroying dopamine nerve fibers. Brain Res 303:359–364

    Article  PubMed  Google Scholar 

  • Satinder KP, Sterling JW (1983) Differential effects of pre- and/or postnatald-amphetamine on avoidance response in genetically selected lines of rats. Neurobehav Toxicol Teratol 5:315–320

    PubMed  Google Scholar 

  • Sato M, Fujiwara Y (1986) Behavioral and neurochemical changes in pups prenatally exposed to methamphetamine. Brain Dev 8:390–396

    PubMed  Google Scholar 

  • Seiden LS, Kleven MS (1989) Methamphetamine and related drugs: toxicity and resulting behavioral changes in response to pharmacological probes. NIDA Res Monogr 94:146–160

    PubMed  Google Scholar 

  • Seiden LS, Vosmer G (1984) Formation of 6-hydroxydopamine in caudate nucleus of the rat brain after a single large dose of methylamphetamine. Pharmacol Biochem Behav 21:29–31

    Article  PubMed  Google Scholar 

  • Seiden LS, Fischman MW, Schuster CR (1975/1976) Long-term methamphetamine-induced changes in brain catecholamines in tolerant rhesus monkeys. Drug Alcohol Depend 1:215–219

    Article  Google Scholar 

  • Seliger DL (1973) Effects of prenatal administration of d-amphetamine on rat offspring activity and passive avoidance learning. Physiol Psychol 1:273–280

    Google Scholar 

  • Sonsalla PK, Nicklas WJ, Heikkila RE (1989) Role for excitatory amino acids in methamphetamine induced dopaminergic toxicity. Science 243:398–400

    PubMed  Google Scholar 

  • Sonsalla PK, Riordan DE, Heikkila RE (1991) Competitive and noncompetitive antagonists at N-methyl-d-aspartate receptors protect against methamphetamine-induced dopaminergic damage in mice. J Pharmacol Exp Ther 256[2]:506–512

    PubMed  Google Scholar 

  • Vorhees CV (1983) Fetal anticonvulsant syndrome in rats: dose- and period-response relationships of prenatal diphenylhydantoin, trimethadione, and phenobarbital exposure on the structural and functional development of the offspring. J Pharmacol Exp Ther 227:274–287

    PubMed  Google Scholar 

  • Vorhees CV (1985) Behavioral effects of prenatald-amphetamine in rats: a parallel trial to the Collaborative Behavioral Teratology study. Neurobehav Toxicol Teratol 7:709–716

    PubMed  Google Scholar 

  • Vorhees CV (1987) Maze learning in rats: A comparison of performance in two water mazes in progeny prenatally exposed to different doses of phenytoin. Neurotoxicol Teratol 9:235–241

    Article  PubMed  Google Scholar 

  • Vorhees CV, Acuff-Smith KD (1990) Prenatal methamphetamine-induced anophthalmia in rats. Neurotoxicol Teratol 12:409

    Article  PubMed  Google Scholar 

  • Vorhees CV, Fernandez K (1986) Effects of short-term prenatal alcohol on maze, activity, and olfactory orientation performance in rats. Neurobehav Toxicol Teratol 8:23–28

    PubMed  Google Scholar 

  • Vorhees CV, Fernandez K, Dumas RM, Haddad RK (1984) Pervasive hyperactivity and long-term learning impairments in rats with induced micrencephaly from prenatal exposure to methylazoxy-methanol. Dev Brain Res 15:1–10

    Article  Google Scholar 

  • Vorhees CV, Weisenburger WP, Acuff-Smith KD, Minck DR (1991) An analysis of factors influencing complex water maze learning in rats: Effects of task complexity, path order and escape assistance on performance following prenatal exposure to phenytoin. Neurotoxicol Teratol 13:213–222

    Article  PubMed  Google Scholar 

  • Vorhees CV, Acuff-Smith KD, Minck DR, Butcher RE (1992) A method for measuring locomotor behavior in rodents: contrastsensitive computer-controlled video tracking activity assessment in rats. Neurotoxicol Teratol 14:43–49

    Article  PubMed  Google Scholar 

  • Wagner GC, Seiden LS, Schuster CR (1979) Methamphetamine induced changes in brain catecholamines in rats and guinea pigs. Drug Alcohol Depend 40:435–438

    Article  Google Scholar 

  • Wagner GC, Ricaurte GA, Seiden LS, Schuster CR, Miller RJ, Westley J (1980) Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine. Brain Res 181:151–160

    Article  PubMed  Google Scholar 

  • Wagner GC, Schuster CR, Seiden LS (1981) Neurochemical consequences following administration of CNS stimulants to the neonatal rat. Pharmacol Biochem Behav 14:117–119

    Article  PubMed  Google Scholar 

  • Wagner GC, Carelli RM, Jarvis MF (1985) Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats. Res Commun Chem Pathol Pharmacol 47:221–228

    PubMed  Google Scholar 

  • Yamamoto T, Takano R, Egashire T, Tamanaka T, Terada M (1989) Simultaneous determination of methamphetamine and its metabolites in monkey urine by gas chromatography/mass spectrometry with selected ion monitoring. J Anal Toxicol 13:117–119

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Children's Hospital Research Foundation, and Department of Pediatrics, University of Cincinnati, 45229, Cincinnati, OH, USA

    Karen D. Acuff-Smith & Charles V. Vorhees

  2. Laboratory of Behavioral Pharmacology (Bldg 135), Loyola University Medical Center, 60153, Maywood, IL, USA

    Magdalena George & Stanley A. Lorens

Authors
  1. Karen D. Acuff-Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magdalena George
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stanley A. Lorens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charles V. Vorhees
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Acuff-Smith, K.D., George, M., Lorens, S.A. et al. Preliminary evidence for methamphetamine-induced behavioral and ocular effects in rat offspring following exposure during early organogenesis. Psychopharmacology 109, 255–263 (1992). https://doi.org/10.1007/BF02245871

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245871

Key words

Search

Navigation