Cocaine and development A retrospective perspective

Spear, Linda P.; Silveri, Marisa M.; Casale, Marc; Katovic, Nina; Campbell, James; Douglas, Lewis A.

doi:10.1016/s0892-0362(02)00194-0

Cited by 42 publications

(33 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If CS exposure or rearing by CS dams alone was sufficient to have an effect on these pups we would have also expected to see main effects of rearing or exposure, but we did not. Any behavioral differences between saline treated and UN dams probably resulted from the stress of the pair feeding procedure or injections, as previously suggested [26,44,48]. Regardless of these limitations, these findings are interesting additions to the animal literature on cocaine exposure and rearing effects on subsequent behavior in both genders.…”

Section: Discussionsupporting

confidence: 55%

Cocaine disrupts pup-induced maternal behavior in juvenile and adult rats

Johns

McMurray

Hofler

et al. 2007

Neurotoxicology and Teratology

View full text Add to dashboard Cite

Impaired onset of maternal behavior in first generation rat dams was previously correlated with rearing by cocaine-treated dams and prenatal cocaine exposure. Pup-induced maternal behavior in non-lactating rats has not been examined with regard to cocaine exposure and rearing conditions. First generation male and female juveniles and young adult males reared by cocaine-treated or control dams and prenatally exposed to either cocaine or control conditions were tested for pup-induced maternal behavior at postnatal days 28 and 60. We now report disruptions in pup-induced maternal behavior in both 28 and 60 day old first generation offspring attributable to rearing condition and prenatal cocaine exposure.

show abstract

Section: Discussionsupporting

confidence: 55%

Cocaine disrupts pup-induced maternal behavior in juvenile and adult rats

Johns

McMurray

Hofler

et al. 2007

Neurotoxicology and Teratology

View full text Add to dashboard Cite

show abstract

“…Although the results are conflicting, it has been shown that female offspring are generally less sensitive in manifestation of cardiovascular disease caused by adverse prenatal stimuli (7). Sex differences in adult offspring, with males often being more susceptible than females on a diversity of measures to the effects of prenatal cocaine exposure in the rat, have been demonstrated consistently (2,11,25,35,36). Whereas the stage of the estrous cycle of the female rats at the time of experiments was not determined, future studies are needed to investigate further the mechanisms of the sex dichotomy observed in the present study and to test for a role of sex steroid hormones in male and female gonadectomized rats.…”

Section: Discussionmentioning

confidence: 99%

Prenatal cocaine exposure abolished ischemic preconditioning-induced protection in adult male rat hearts: role of PKCε

Meyer¹,

Zhang²,

Zhang³

2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

natal cocaine exposure in rats resulted in decreased PKCε protein expression in the heart of adult male but not female offspring. The present study determined its functional consequence of inhibiting cardioprotection mediated by ischemic preconditioning. Pregnant Sprague-Dawley rats were administered intraperitoneally saline or cocaine (30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) from day 15 to day 21 of gestational age. Hearts were isolated from 3-mo-old offspring and were subjected to ischemia and reperfusion injury in a Langendorff preparation, with or without prior ischemic preconditioning. Preischemic values of left ventricular function were the same between the saline control and cocaine-treated animals. Ischemic preconditioning of two episodes of 5-min ischemia significantly decreased infarct size and enhanced postischemic functional recovery of the left ventricle in the saline control animals. This ischemic preconditioning was associated with increased phospho-PKCε, but not phospho-PKC␦, levels and was blocked by a PKCε translocation inhibitor peptide. Prenatal cocaine treatment abolished the ischemic preconditioning-mediated increase in phospho-PKCε and cardioprotection in the heart of male offspring. In contrast, the cardioprotective effect was fully maintained in female offspring that were exposed to cocaine before birth. The results suggest that prenatal cocaine exposure causes a sex-specific loss of cardioprotection by ischemic preconditioning in adult offspring, which is most likely due to fetal programming of PKCε gene repression, resulting in a downregulation of PKCε function in the heart of adult male offspring.

show abstract

“…In utero cocaine exposure has limited effects on cognitive performance in adult rodents (4)(5)(6), but adolescent and adult cocaine use is associated with poor inhibitory control, inflexible behavior, and drug-related compulsivity. Here, we use an animal model of late-onset dendritic simplification to test the hypothesis that the transition from dendritic refinement and synaptic pruning processes that occur in the adolescent prefrontal cortex (PFC), to the dendrite stabilization processes occurring in the adult PFC, is a period of vulnerability to cocaine.…”

mentioning

confidence: 99%

Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine

Gourley

Koleske

Taylor

2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Adolescence is characterized by increased vulnerability to developing neuropsychiatric disorders and involves a period of prefrontal cortical dendritic refinement and synaptic pruning that culminates in cytoskeletal stabilization in adulthood. The Abl-related gene (Arg) acts through p190RhoGAP to inhibit the RhoA GTPase and stabilize cortical dendritic arbors beginning in adolescence. Cortical axons, dendrites, and synapses develop normally in Argdeficient (arg ؊/؊ ) mice, but adult dendrites destabilize and regress; thus, arg ؊/؊ mice present a model of adolescent-onset dendritic simplification. We show that arg ؊/؊ mice are impaired in a reversal task and that deficits are grossly exacerbated by low-dose cocaine administration. Although ventral prefrontal dopamine D2 receptor levels predict ''perseverative'' error counts in wild-type mice, no such relationship is found in arg ؊/؊ mice. Moreover, arg ؊/؊ mice are insensitive to the disruptive effects of the D2/D3 antagonist haloperidol in reversal but show normal sensitivity to its locomotor-depressant actions. Arg deficiency and orbitofrontal cortical Arg inhibition via STI-571 infusion also enhance the psychomotor stimulant actions of cocaine. These findings provide evidence that stabilization of dendritic structure beginning in adolescence is critical for the development of adaptive and flexible behavior after cocaine exposure.A dolescence is a critical period of maturation for corticostriatal neurocircuitry and is characterized by increased risk taking, novelty seeking, and vulnerability to addictive drugs that, with repeated use, are associated with cognitive dysfunction in adulthood (1-3). In utero cocaine exposure has limited effects on cognitive performance in adult rodents (4-6), but adolescent and adult cocaine use is associated with poor inhibitory control, inflexible behavior, and drug-related compulsivity. Here, we use an animal model of late-onset dendritic simplification to test the hypothesis that the transition from dendritic refinement and synaptic pruning processes that occur in the adolescent prefrontal cortex (PFC), to the dendrite stabilization processes occurring in the adult PFC, is a period of vulnerability to cocaine.Numerous proteins regulate cortical dendrite development; to date, however, only a few have been implicated in cytoskeletal stability in adolescence and adulthood, serving primarily to antagonize inherent cytoskeletal retraction machinery. For example, activation of the master cytoskeletal regulator, RhoA (Rho), induces neurite retraction, a process required for pruning and refining neuronal connections during development. Rho activation in mature neurons, however, leads to synapse loss and dendritic regression in a wide variety of experimental systems (7-9). Recent studies have identified a Rho inhibitory pathway involving integrin adhesion receptors, the Abl family tyrosine kinase, Arg, and the Rho inhibitor, p190RhoGAP, that acts in dendritic spines of late adolescent mice to maintain synapses and promote dendrite stabi...

show abstract

Cocaine and development A retrospective perspective

Cited by 42 publications

References 49 publications

Cocaine disrupts pup-induced maternal behavior in juvenile and adult rats

Cocaine disrupts pup-induced maternal behavior in juvenile and adult rats

Prenatal cocaine exposure abolished ischemic preconditioning-induced protection in adult male rat hearts: role of PKCε

Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine

Contact Info

Product

Resources

About