Abstract
Rationale
Although the influence of gestational cocaine exposure on offspring has been the focus of a sustained research effort, the effect of preconception cocaine self-administration by dams on progeny has received far less attention.
Method
In the current study, adult female rats were allowed to self-administer cocaine 2 h a day for 60 days and then after a 10-day wash out period, bred to naïve males. Maternal behavior was measured in dams until weaning. When male and female progeny reached adulthood, anxiety-like behavior, memory, and cocaine self-administration were assessed in separate cohorts of rats.
Results
Despite a total of at least 30 days of cocaine abstinence, the quality of maternal behaviors was negatively affected by previous cocaine exposure as reflected by less time spent with pups as well as an excess of other maladaptive maternal behaviors. Measures of anxiety-like behavior and memory were not affected by maternal cocaine intake in either male or female offspring. In contrast, male, but not female, the progeny of dams exposed to cocaine showed increased reinforcing efficacy of cocaine as measured by cocaine self-administration under a progressive ratio schedule. The fact that cocaine self-administration was influenced only in the male offspring of cocaine-exposed dams argues against this phenotype being linked to altered maternal behavior, although this possibility cannot be ruled out completely.
Conclusions
Collectively, these results indicate that preconception cocaine self-administration by dams results in the relatively selective enhancement of cocaine addiction-like behavior in male offspring.
Similar content being viewed by others
References
Betancourt LM, Yang W, Brodsky NL, Gallagher PR, Malmud EK, Giannetta JM, Farah MJ, Hurt H (2011) Adolescents with and without gestational cocaine exposure: longitudinal analysis of inhibitory control, memory and receptive language. Neurotoxicol Teratol 33:36–46
Byrnes EM (2005) Transgenerational consequences of adolescent morphine exposure in female rats: effects on anxiety-like behaviors and morphine sensitization in adult offspring. Psychopharmacology 182:537–544
Byrnes JJ, Babb JA, Scanlan VF, Byrnes EM (2011) Adolescent opioid exposure in female rats: transgenerational effects on morphine analgesia and anxiety-like behavior in adult offspring. Behav Brain Res 218:200–205
Byrnes JJ, Johnson NL, Schenk ME, Byrnes EM (2012) Cannabinoid exposure in adolescent female rats induces transgenerational effects on morphine conditioned place preference in male offspring. J Psychopharmacol 26:1348–1354
Champagne FA, Francis DD, Mar A, Meaney MJ (2003) Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol Behav 79:359–371
Dalle Molle R, Portella AK, Goldani MZ, Kapczinski FP, Leistner-Segal S, Salum GA, Manfro GG, Silveira PP (2012) Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels. Transl Psychiatry 2:e195
Dow-Edwards D (2011) Translational issues for prenatal cocaine studies and the role of environment. Neurotoxicol Teratol 33:9–16
Febo M, Ferris CF (2007) Development of cocaine sensitization before pregnancy affects subsequent maternal retrieval of pups and prefrontal cortical activity during nursing. Neuroscience 148:400–412
Fischer DK, Rice RC, Martinez Rivera A, Donohoe M, Rajadhyaksha AM (2017) Altered reward sensitivity in female offspring of cocaine-exposed fathers. Behav Brain Res 332:23–31
Forwood SE, Winters BD, Bussey TJ (2005) Hippocampal lesions that abolish spatial maze performance spare object recognition memory at delays of up to 48 h. Hippocampus 15:347–355
Hao Y, Huang W, Nielsen DA, Kosten TA (2011) Litter gender composition and sex affect maternal behavior and DNA methylation levels of the oprm1 gene in rat offspring. Front Psychiatry 2:21
He F, Lidow IA, Lidow MS (2006) Consequences of paternal cocaine exposure in mice. Neurotoxicol Teratol 28:198–209
Hurt H, Betancourt LM, Malmud EK, Shera DM, Giannetta JM, Brodsky NL, Farah MJ (2009) Children with and without gestational cocaine exposure: a neurocognitive systems analysis. Neurotoxicol Teratol 31:334–341
Killinger CE, Robinson S, Stanwood GD (2012) Subtle biobehavioral effects produced by paternal cocaine exposure. Synapse 66:902–908
Le Q, Yan B, Yu X, Li Y, Song H, Zhu H, Hou W, Ma D, Wu F, Zhou Y, Ma L (2017) Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour. Nat Commun 8:15527
Lidow MS (2003) Consequences of prenatal cocaine exposure in nonhuman primates. Brain Res Dev Brain Res 147:23–36
Liu D, Diorio J, Day JC, Francis DD, Meaney MJ (2000) Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci 3:799–806
Livy DJ, Maier SE, West JR (2004) Long-term alcohol exposure prior to conception results in lower fetal body weights. Birth Defects Res B 71:135–141
McCarthy DM, Kabir ZD, Bhide PG, Kosofsky BE (2014) Effects of prenatal exposure to cocaine on brain structure and function. Prog Brain Res 211:277–289
Mets B, Diaz J, Soo E, Jamdar S (1999) Cocaine, norcocaine, ecgonine methylester and benzoylecgonine pharmacokinetics in the rat. Life Sci 65:1317–1328
Mumby DG (2001) Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats. Behav Brain Res 127:159–181
Nephew BC, Febo M (2010) Effect of cocaine sensitization prior to pregnancy on maternal care and aggression in the rat. Psychopharmacology 209:127–135
Oliveira AM, Hawk JD, Abel T, Havekes R (2010) Post-training reversible inactivation of the hippocampus enhances novel object recognition memory. Learn Mem 17:155–160
Olsen CM, Duvauchelle CL (2006) Prefrontal cortex D1 modulation of the reinforcing properties of cocaine. Brain Res 1075:229–235
Ramsay M (2010) Genetic and epigenetic insights into fetal alcohol spectrum disorders. Genome Med 2:27
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
Sanchez CJ, Bailie TM, Wu WR, Li N, Sorg BA (2003) Manipulation of dopamine d1-like receptor activation in the rat medial prefrontal cortex alters stress- and cocaine-induced reinstatement of conditioned place preference behavior. Neuroscience 119:497–505
Dos Santos JF, de Melo Bastos Cavalcante C, Barbosa FT, Gitai DLG, Duzzioni M, Tilelli CQ, Shetty AK, de Castro OW (2018) Maternal, fetal and neonatal consequences associated with the use of crack cocaine during the gestational period: a systematic review and meta-analysis. Arch Gynecol Obstet 298:487–503
Sasaki A, Constantinof A, Pan P, Kupferschmidt DA, McGowan PO, Erb S (2014) Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine and transcriptional regulation of the dopamine D1 receptor in adult male offspring. Behav Brain Res 265:163–170
Schmidt HD, Famous KR, Pierce RC (2009) The limbic circuitry underlying cocaine seeking encompasses the PPTg/LDT. Eur J Neurosci 30:1358–1369
Sun W, Rebec GV (2005) The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats. Psychopharmacology 177:315–323
Szyf M, Weaver I, Meaney M (2007) Maternal care, the epigenome and phenotypic differences in behavior. Reprod Toxicol 24:9–19
Vassoler FM, Schmidt HD, Gerard ME, Famous KR, Ciraulo DA, Kornetsky C, Knapp CM, Pierce RC (2008) Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats. J Neurosci 28:8735–8739
Vassoler FM, Johnson NL, Byrnes EM (2013a) Female adolescent exposure to cannabinoids causes transgenerational effects on morphine sensitization in female offspring in the absence of in utero exposure. J Psychopharmacol 27:1015–1022
Vassoler FM, White SL, Schmidt HD, Sadri-Vakili G, Pierce RC (2013b) Epigenetic inheritance of a cocaine-resistance phenotype. Nat Neurosci 16:42–47
Vassoler FM, Byrnes EM, Pierce RC (2014) The impact of exposure to addictive drugs on future generations: physiological and behavioral effects. Neuropharmacology 76(Pt B):269–275
Vassoler FM, Wright SJ, Byrnes EM (2016) Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring. Neuropharmacology 103:112–121
Vassoler FM, Oliver DJ, Wyse C, Blau A, Shtutman M, Turner JR, Byrnes EM (2017) Transgenerational attenuation of opioid self-administration as a consequence of adolescent morphine exposure. Neuropharmacology 113:271–280
Vassoler FM, Toorie AM, Byrnes EM (2018) Increased cocaine reward in offspring of females exposed to morphine during adolescence. Psychopharmacology
Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854
White SL, Vassoler FM, Schmidt HD, Pierce RC, Wimmer ME (2016) Enhanced anxiety in the male offspring of sires that self-administered cocaine. Addict Biol 21:802–810
Wimmer ME, Briand LA, Fant B, Guercio LA, Arreola AC, Schmidt HD, Sidoli S, Han Y, Garcia BA, Pierce RC (2017) Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny. Mol Psychiatry
Funding
This work was supported by the following grants from the National Institutes of Health: R01 DA33641 (RCP), T32 DA28874 (SES-J), and K01 DA39308 (MEW).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Fant, B., Wimmer, M.E., Swinford-Jackson, S.E. et al. Preconception maternal cocaine self-administration increases the reinforcing efficacy of cocaine in male offspring. Psychopharmacology 236, 3429–3437 (2019). https://doi.org/10.1007/s00213-019-05307-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-019-05307-y