Interactive effects of prenatal cocaine and nicotine exposure on maternal toxicity, postnatal development, and behavior in the rat
Abstract
Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without altering maternal gestational parameters and/or fetal viability. Exposure of Sprague-Dawley rats to combined high-dose C (20 mg/kg) and high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus that that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal development, and behavior of the offspring following drug exposure to either high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS), or both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by sc injection. Saline-injected dams, fitted with saline-fitted pumps (SS), and untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in maternal variables were limited to a 10-15% decrease in food consumption in NC and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal treatment, as was offspring body weight during the first four postnatal weeks. However, the development of surface righting was delayed inC CS pups, and only CS offspring were underresponsive to the stimulatory effects of dopamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring showed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D1 and D2 binding in the caudate nucleus were not observed. The combination of N and C did not exacerbate any of the behavioral changes seen in CS offspring. These results support the hypothesis that C is a behavioral teratogen in rodents, and suggest that in the present model, nicotine can mitigate some of the consequences of in utero exposure to cocaine.
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Rodent studies suggest prenatal nicotine exposure delays reflex maturation, including negative geotaxis and surface righting, and causes long-lasting changes in filtering auditory information.
“rodent studies suggest that prenatal nicotine exposure delays maturation of reflexes, including negative geotaxis and surface righting (measures of limb coordination and locomotor development), as well as causing long-lasting alterations in filtering auditory information.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [177]
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Cites
The effects of prenatal nicotine on radial-arm maze performance in rats
Sorenson, C. A., Raskin, L. A., & Suh, Y. (1991) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(91)90117-k · Cited by 97 · see citing works
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“Similarly, Sobrian et al. (1995) showed that cocaine (20 mg/kg) produces the delayed effect of righting on surface.”
Nitric Oxide and Oxidative Stress in the Brain of Rats Exposed In Utero to Cocaine
Bashkatova, V., Meunier, J., Vanin, A., & Maurice, T. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1369.061 · Cited by 36
Cocaine-Induced Neurodevelopmental Deficits and Underlying Mechanisms
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“While it is clear that drugs of abuse impact maternal behavior, there is a body of literature that also indicates that withdrawal from such drugs also significantly alters maternal care and disrupts the maternal-offspring dyad (Johns et al., 1994; Kinsley et al., 1994; Sobrian et al., 1995; McMurray et al., 2008).”
Ellis-Hutchings, R., Rasoulpour, R., Terry, C., Carney, E., & Billington, R. (2014) · Critical Reviews in Toxicology · doi:10.3109/10408444.2014.910752 · Cited by 26
“…nicotine exposure has been demonstrated to alter fetal lung development in rats (Maritz and van Wyk 1997) and associated neuronal nAChR expression in primates (Sekhon et al. 1999), it paradoxically does not cause neonatal death during normoxic conditions in rats (Geller 1959, Sobrian et al. 1995).”
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“…et al., 1990, 1995; Heyser et al., 1992; Nelson et al., 1998; Johns et al., 2005; McMurray et al., 2008a), and is evident during both early (Sobrian et al., 1990, 1995; Tonkiss et al., 1995; Vernotica et al., 1996; Nelson et al., 1998), and mid (Heyser et al., 1992; Tonkiss et al., 1995;…”
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Self-citationEffects of pre-and neonatal nicotine exposure in rodents: inconsistent evidence
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“One possibility for this may be the age of pups at which the righting reflex test was conducted, whereby in the study by Sobrian et al. [40] this reflex was measured on postnatal day three, whereas in the study by Ajarem and Ahmad [33], the righting reflex was assessed on the first postnatal day.”
Influential
- Authors
- Sobrian, S. K., Ali, S. F., Slikker, W., & Robert Holson, R.
- Affiliations
- Howard University (US)
- National Center for Toxicological Research (US)
- Venue
- Molecular Neurobiology
- Published
- 1995-08
- Volume
- 11
- Issue
- 1-3
- Pages
- 121-143
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W1977895643
- Cited by
- 30
- References
- 0
- Citations by year
- 2026: 1 · 2019: 1 · 2018: 2 · 2016: 2 · 2014: 2 · 2013: 2
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- prenatal cocaine exposure, prenatal nicotine exposure, maternal toxicity, fetal viability, pregnancy outcomes, postnatal development, righting reflex, stereotypy, spontaneous alternation, caudate nucleus
- MeSH terms
- Aging, Animals, Avoidance Learning, Body Weight, Caudate Nucleus, Cocaine, Dose-Response Relationship, Drug, Drug Interactions, Female, Fetal Blood, Motor Activity, Nicotine, Pregnancy, Pregnancy, Animal, Prenatal Exposure Delayed Effects, Reference Values, Reflex, Sex Characteristics, Reflex, Startle, Stereotyped Behavior, Weight Gain, Rats, Sprague-Dawley, Receptors, Dopamine D1, Receptors, Dopamine D2, Maze Learning, Rats
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