Maternal Separation and Handling Affects Cocaine Self-Administration in Both the Treated Pups as Adults and the Dams

Abstract

Repeated maternal separation of pups from dams is often used as an early life stressor that causes profound neurochemical and behavioral changes in the pups that persist into adulthood. The effects of maternal separation on both the dams and the treated pups as adults on cocaine self-administration were examined using four separation conditions: 15-or 180-min separation (MS15 and MS180), brief handling without separation (MS0), and a nonhandled group (NH). The separations and handling occurred daily on postnatal days 2 to 15. The acquisition of cocaine self-administration (0.0625-1.0 mg/kg/infusion) was evaluated in the treated pups as adults. The MS180 group acquired cocaine self-administration at the lowest dose tested (0.0625 mg/kg/infusion), whereas the MS15s did not respond for cocaine at rates greater than that seen with saline administration. The NH group received the greatest number of infusions and intake at the highest doses. After self-administration, no differences were observed between groups in activity of two liver carboxylesterases involved in the inactivation of cocaine, ES10 and ES4. Maternal separation affected cocaine self-administration in the dams as well. Although there was an overall significant affect of treatment on cocaine self-administration, the length of separation (15 or 180 min) did not affect cocaine self-administration on the dams. The MS0 dams averaged a greater number of infusions per session than NH group during the 1st week of acquisition. These data suggest that in addition to the profound changes that occur in pups as result of maternal separation, the dams are also susceptible to alterations in behaviors.Traumatic or stressful events experienced in childhood can have profound behavioral effects in adults. Therefore, it is not surprising that early adverse events in humans are associated with increased vulnerability to drug abuse as adults. McFarlane et al. (2005) found an association of adverse early life experiences with nicotine dependence. Felitti et al. (1998) found a strong relationship between household dysfunction during childhood and drug abuse, and others have had similar results (Dube et al., 2003). Because of the relatively common and serious nature of this problem, developing an animal model has been important.Animal models of early life stress, such as maternal separation and neonatal isolation, have been developed in an attempt to elucidate the neurochemical and behavioral alterations resulting from exposure to the early life stressor. In animal models, perinatal stress affects behavioral response to various drugs of abuse. Neonatal isolation and prolonged maternal separation alter the self-administration of cocaine in rats (Matthews et al., 1999;Flagel et al., 2003;Kosten et al., 2004;Zhang et al., 2005). Early life stress also alters conditioned place preference for amphetamine (Campbell and Spear, 1999), cocaine-induced locomotor activity (Brake et al., 2004), behavioral sensitization to cocaine (Li et al., 2003), ethanol preference and consumptio...

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…Most studies show an increase (Zimmerberg and Shartrand, 1992;Kehoe et al, 1996Kehoe et al, , 1998Pryce et al, 2001;Brake et al, 2004;Marin and Planeta, 2004;Kikusui et al, 2005) or no effect (Lehmann et al, 1998;Li et al, 2003;Marmendal et al, 2004;Kosten et al, 2005a,c;Hensleigh et al, 2011) compared with stimulant effects in controls, whereas others show a decrease (Matthews et al, 1996a;Moffett et al, 2006). Factors that likely account for these differences are drug history before acute stimulant administration, doses of stimulant tested, and sex.…”

“…cocaine (Kosten et al, 2000(Kosten et al, , 2004Zhang et al, 2005;Moffett et al, 2006), although one study using a 24-h discrete trial reinforcement schedule found no effect of maternal separation in cocaine self-administration in either male or female rats (Lynch et al, 2005). In females, Psychosocial Influences and Abused Drugs increases in cocaine self-administration are obtained (Matthews et al, 1999;Kosten et al, 2006;Moffett et al, 2006); however, decreases in intake also have been reported (Kosten et al, 2004;Matthews et al, 1999). This sex dependency is corroborated by other evidence showing that maternal separation increases amphetamine reward as measured by intracranial brain stimulation threshold in male rats (Der-Avakian and Markou, 2010) but not in female rats (Matthews and Robbins, 2003).…”

Early Postnatal Stress Alters Place Conditioning to Both μ- and κ-Opioid Agonists

“…In general, MS offspring exhibit increased intake of sucrose solution and acquisition of cocaine self-administration, and they show a decreased response to intracranial self-stimulation compared to NH offspring (Matthews and Robbins, 2003;Michaels and Holtzman, 2006;Moffett et al, 2006;Michaels et al, 2007). Although the effect of MS on the above measures has been investigated, no one has explored how MS affects place conditioning to either -or -opioid agonists.…”

Ontogênese, estresse e dependência de substâncias psicoativas

“…Entretanto, é importante ressaltar que a presença de sensibilização na adolescência é altamente relevante, uma vez que indica que perturbações neonatais podem aumentar a vulnerabilidade ao desenvolvimento da dependência de cocaína nessa fase do desenvolvimento. Moffett et al (2006) avaliaram os efeitos da separação materna na auto-administração de cocaína. Esses autores demonstraram que ratos adultos separados das mães por 6 horas entre os dias pós-natal 2 a 15 adquiriram autoadministração de cocaína em doses menores do que aquelas necessárias para produzir a aquisição em ratos não expostos ao estresse.…”