Gestational treatment with cocaine and fluoxetine alters oxytocin receptor number and binding affinity in lactating rat dams

Johns, Josephine M.; Lubin, Deborah A.; Walker, Cheryl H.; Joyner, Paul; Middleton, Christopher; Hofler, Vivian E.; McMurray, Matthew S.

doi:10.1016/j.ijdevneu.2004.03.002

Cited by 28 publications

(29 citation statements)

References 64 publications

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“…Unfortunately, we found no such studies investigating MA effects on oxytocin levels. However, there are studies (Elliott et al, 2001;Johns et al, 2004;Johns, Lubin, Walker, Meter, & Mason, 1997) showing that acute or chronic cocaine administration alters oxytocin levels and the number and binding affinity of oxytocin receptors in brain areas related to nursing and maternal behavior. Thus, it might be that MA has similar effects on oxytocin as cocaine, because of their similar pharmacokinetics.…”

Section: Discussionmentioning

confidence: 99%

Effect of methamphetamine exposure during prenatal and preweaning periods lasts for generations in rats

Šlamberová

Pometlová

Rokyta

2007

Developmental Psychobiology

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Our previous studies demonstrated that methamphetamine (MA) administration during gestation and/or lactation affects maternal behavior in rats and that birth weight and sensory-motor coordination of their pups are also influenced. The present study tested the hypothesis that the effect of MA induces long-term changes affecting second generation of rats that were not exposed to the drug. Adult females exposed during prenatal and preweaning periods to 5 mg/kg MA daily, were examined for regularity of estrous cycle and mated with stimulus, unexposed males. Dams (nontreated absolute control, saline- and MA-exposed) were observed with their pups in two tests of maternal behavior (observational and retrieval tests). Their pups were further tested throughout the preweaning period to examine their development. Our data demonstrate that MA-exposed mothers displayed more nursing, were more often in the nest and in contact with their pups, and were faster in retrieving their pups than saline-exposed and/or control mothers. There were no differences in litter characteristics, birth weight and weight gain of pups between groups. Interestingly, pups from mothers exposed to MA during prenatal and preweaning period had impaired sensory-motor coordination. They achieved righting reflex in mid-air later than both control groups. Additionally, they had more falls in rotarod and bar-holding tests than pups from both control and saline-exposed mothers. In homing performance, pups from MA- and saline-exposed dams learned slower to return to the home box than pups from control dams. Thus, the present study demonstrates that MA abused by mothers may affect two generations of their offspring.

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Section: Discussionmentioning

confidence: 99%

Effect of methamphetamine exposure during prenatal and preweaning periods lasts for generations in rats

Šlamberová

Pometlová

Rokyta

2007

Developmental Psychobiology

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“…Most findings to date are reported for lactating dams during the earlier postpartum period at more moderate doses of cocaine, with some data available for the later postpartum period at higher doses (Heyser et al 1992). Interestingly, MA alterations following cocaine-treatment in rats are associated with alterations in brain levels of the neuropeptide oxytocin (Johns et al 1997a;Elliott et al 2001), as well as oxytocin receptor binding and affinity in the hypothalamus and limbic system (Johns et al 2004;Jarrett et al 2006). It has been suggested (Johns et al 1994b;Johns et al 1998b;Lubin et al 2003) that cocaine-induced oxytocin system alterations may be at least partially responsible for alterations in MA behavior in cocainetreated rats.…”

Section: Introductionmentioning

confidence: 99%

Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams

McMurray

Joyner

Middleton

et al. 2008

Stress

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Gestational cocaine treatment results in significantly increased maternal aggression towards an intruder by postpartum day six, while acute postpartum treatment dose dependently decreases maternal aggressive (MA) behavior. Both increased and decreased aggression in the cocainetreated dams are correlated with either decreased or increased levels of oxytocin in the amygdala, respectively. The current study was an effort to determine whether the effect of gestational cocaine on maternal aggression is transient or would continue into the postpartum period; whether an intermittent cocaine treatment regimen, which incorporates gestational and postpartum intermittent cocaine treatment, would differ from chronic daily gestational treatment; and finally, whether next generation female offspring of cocaine-treated or control dams would have altered MA behavior and oxytocin system changes attributable to either prenatal drug exposure, rearing condition or both. We now report no increase in maternal aggression following chronic gestational treatment and significantly lower levels of aggression in intermittently treated dams on postpartum day eight, with no significant effects in either group on postpartum day 12. Young adult female offspring of the cocaine-treated and control dams, who reared their own natural litters and were tested on postpartum day eight for maternal aggression, had higher levels of maternal aggression towards an intruder attributable to both prenatal cocaine exposure and rearing condition. Higher aggression in cocaine-reared next generation dams was associated with lower levels of oxytocin in the amygdala. Intergenerational effects of cocaine were apparent with respect to aggression and oxytocin system changes.

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“…Pedersen et al (1982) demonstrated that oxytocin administration to ovar-iectomized rats can induce and perpetuate maternal behavior, while Lubin et al (2003b) demonstrated that oxytocin antagonist administration into the central amygdala increases maternal aggression. Johns et al (2004) found that gestational treatment with fluoxetine (a serotonin reuptake inhibitor) resulted in a reduction in oxytocin receptor affinity and an upregulation of oxytocin receptor number in the amygdala. Several brain regions are suggested as being relevant to maternal behavior and/or aggression in the rat, including the medial preoptic area (MPOA), ventral tegmental area (VTA), hippocampus, and amygdala, and reductions in oxytocin in these areas correlate with deficits in maternal behavior and/or aggression (Ferris et al, 1992;Gaffori and Le Moal, 1979;Johns et al, 1995Johns et al, , 1997Kimble et al, 1967;Lubin et al, 2003b;Numan and Smith, 1984;Numan, 1994a,b).…”

Section: Introductionmentioning

confidence: 99%

The effects of dopaminergic/serotonergic reuptake inhibition on maternal behavior, maternal aggression, and oxytocin in the rat

Johns

Joyner

McMurray

et al. 2005

Pharmacology Biochemistry and Behavior

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Studies using dopaminergic and serotonergic agonists or antagonists implicate involvement of these systems in various aspects of early maternal behavior and postpartum aggression towards an intruder in rats, both of which are associated with the presence of oxytocin in specific brain regions. It is unclear however, if or how long-term uptake inhibition of either neurotransmitter system alone or in combination, affects oxytocin system dynamics or maternal behavior/ aggression. Pregnant women frequently take drugs (antidepressants, cocaine) that induce longterm reuptake inhibition of dopamine and/or serotonin, thus it is important to understand these effects on behavior and biochemistry. Rat dams were treated throughout gestation with amfonelic acid, fluoxetine, or a combination of both, to investigate effects of reuptake inhibition of dopamine and serotonin systems respectively, on maternal behavior, aggression and oxytocin. The more appetitive aspects of maternal behavior (nesting, licking, touching) and activity were increased by the low dose of amfonelic acid, high dose of fluoxetine, or the high dose combination more than other treatments. Aggression was decreased by amfonelic acid and somewhat increased by fluoxetine. Dopamine uptake inhibition appears to have a strong effect on hippocampal oxytocin levels, while receptor dynamics may be more strongly affected by serotonin uptake inhibition.

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Gestational treatment with cocaine and fluoxetine alters oxytocin receptor number and binding affinity in lactating rat dams

Cited by 28 publications

References 64 publications

Effect of methamphetamine exposure during prenatal and preweaning periods lasts for generations in rats

Effect of methamphetamine exposure during prenatal and preweaning periods lasts for generations in rats

Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams

The effects of dopaminergic/serotonergic reuptake inhibition on maternal behavior, maternal aggression, and oxytocin in the rat

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