Manipulations During the Second, but not the First, Week of Life Increase Susceptibility to Cocaine Self-Administration in Female Rats

Abstract

We compared the effects of manipulations during week 1 vs week 2 of life on the propensity to self-administer cocaine. Pups received daily subcutaneous saline injections, were handled briefly, or remained undisturbed during their respective treatment periods. Animals handled during the second week of life exhibited increased locomotor response to novelty when tested on postnatal day (PND) 48, compared to all other groups. Rats were implanted with jugular catheters on PND 70 and then given the opportunity to self-administer (0.125 mg/kg/infusion) cocaine for 5 consecutive days (1 h sessions). The dose was then raised to 0.25 mg/kg/infusion for 5 days and to 0.5 mg/kg/infusion for the final 5 days of testing. Only animals manipulated during the second week of life acquired drug-taking behavior. These effects were both stimulus-and gender-specific. Females handled during the second week of life acquired cocaine selfadministration (SA) at the lowest dose, and females injected during the second week of life acquired at the intermediate dose. Males injected during the second week of life showed a similar, but more variable, drug-taking pattern. There were no group differences in serum corticosterone response to novelty, although relative to undisturbed animals and those manipulated in the first week of life, female animals manipulated during the second week of life had lower basal expression of hippocampal glucocorticoid receptor mRNA in adulthood. We conclude that the second week of life in the rodent is a sensitive period during which manipulations result in a more vulnerable phenotype for the acquisition of cocaine SA.

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

“…With cocaine self-administration, MS15 male and female rats fail to acquire cocaine self-administration with a unit dose (0.0625 mg/kg per infusion) that supports self-administration in controls and MS180 rats . Further, a protective effect of brief maternal separation against cocaine selfadministration is obtained in MS10 males receiving the separation during the first postnatal week, whereas MS10 females separated briefly during the second, but not the first, postnatal week self-administer more cocaine (Flagel et al, 2003). Thus, sex-and timedependent differences exist in the protective effect of brief maternal separation.…”

Effects of early maternal separation on ethanol intake, GABA receptors and metabolizing enzymes in adult rats

“…Different effects of drugs of abuse have been observed after different conditions of separation. These effects have included alterations in cocaine self-administration (Flagel et al 2003;Matthews et al 1999), cocaine-induced sensitization (Li et al 2003), conditioned place preference for amphetamine (Campbell and Spear 1999), ethanol preference and effects of antidepressants (Huot et al 2001;Ploj et al 2003), responses to morphine (Kalinichev et al 2001(Kalinichev et al , 2002(Kalinichev et al , 2003, conditioned appetitive cues (Matthews et al 1996) and behavioral responses to stress (Meaney et al 1996). In addition, several neurochemical alterations in the dopamine mesolimbic system have been reported that may underlie some of the observed behavioral changes (Brake et al 2004;Hall et al 1999;Meaney et al 2002;Ploj et al 2003).…”

Enhancing glutamatergic transmission during adolescence reverses early-life stress-induced deficits in the rewarding effects of cocaine in rats

“…However, this highly-plastic neuronal environment makes the brain highly susceptible to pathological insult (Bondi et al, 2014;Enoch, 2011;Meyer-Lindenberg and Tost, 2012;O'Connor and Cryan, 2014) including psychological stress which has been well established as predisposing individuals to addictive disorders later in life (De Bellis, 2002;Enoch, 2011;Koob, 2008). Indeed, preclinical studies have demonstrated psychological stress induced early in life can affect reward-function in adulthood; both increasing rewardinduced behavioural-reinforcement (Flagel et al, 2003;Kosten et al, 2000;Matthews et al, 1999) and decreasing reward intake, possibly through anhedonia (Martini and Valverde, 2012;Matthews et al, 1999;Silveira et al, 2010). Thus, a need to clarify the mechanisms by which exposure to a psychological stress can alter drug-intake in adulthood remains.…”