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...

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These data suggest an important role for CRF in the cue- and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior.

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CART (cocaine-and amphetamine-regulated transcript) peptides are peptidergic neurotransmitters that are widely but specifically distributed throughout the brain, gut and other parts of the body. They are found in many brain regions associated with drug addiction including the nucleus accumbens, ventral tegmental area and ventral pallidum. Injections of CART 55-102 into the nucleus accumbens have no effect on basal locomotor activity. However, an injection of CART just before an i.p. injection of cocaine reduces the locomotor activating effects of cocaine. These and other data suggest that CART in the accumbens blunts the effects of cocaine. A hypothesis is that CART is homeostatic in the accumbens and tends to oppose large increases in dopamine signaling. These actions would therefore be able to regulate the effects of some abused drugs such as the psychostimulants.

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