Predictable individual differences in the initiation of cocaine self-administration by rats under extended-access conditions are dose-dependent

Abstract

The present findings indicate that predictable individual differences in cocaine SA under extended access conditions are relevant only at low doses and are surmountable by increasing the available dose of cocaine.

Effects of Cocaine in Rats Exposed to Heroin

“…These data are consistent with studies showing that pre-exposure to morphine can enhance the reinforcing effects of cocaine in a conditioned place preference procedure (Lett, 1989), and with those showing that the activating and reinforcing effects of stimulants share common neural mechanisms (Wise and Bozarth, 1987;Robinson and Berridge, 2003;Spanagel, 1995). They are also consistent with the view that differences in sensitivity to cocaine self-administration become apparent primarily when low doses are used (Deroche et al, 1999;Mantsch et al, 2001; but see Piazza et al, 2000), although it is possible that larger differences would have emerged had we tested the animals for longer periods of time during the test for escalation (Ahmed and Koob, 1999;Ahmed et al, 2000) and during the assessment of the dose-response relationship. Perhaps more importantly, the small degree of crosssensitization between the stimulant effects of heroin and cocaine in this study might have been expected owing to the fact that heroin was administered continuously via a minipump.…”

“…After 1 week, they were tested for cocaine self-administration under three different conditions. These three conditions were chosen on the basis of previous reports indicating that rats with enhanced sensitivity to the behavioral activating effects of stimulants will self-administer more stimulants at low doses, show enhanced escalation of drug intake, and display an upward shift in dose-response for cocaine self-administration (Deroche et al, 1999;Piazza et al, 2000;Mantsch et al, 2001). Thus, in the first condition, the propensity to selfadminister a low dose of cocaine, 0.13 mg/kg/infusion, was assessed over 3 consecutive days in 6-h sessions.…”

Brief Social Defeat Stress: Long Lasting Effects on Cocaine Taking During a Binge and Zif268 mRNA Expression in the Amygdala and Prefrontal Cortex

“…Prolonged access to cocaine engenders neural, endocrine, autonomic, and behavioral adaptations not seen after daily limited access (Markou and Koob, 1991;Parsons et al, 1995;Mutschler and Miczek, 1998;Mantsch et al, 2001;Mutschler et al, 2001). Furthermore, access to cocaine exceeding 12-16 h reveals a transition from regular patterns of responding to behavioral dysregulation (Kreek and Koob, 1998).…”

“…Lower unit doses might have revealed more subtle differences with respect to acquisition (Carroll et al, 2002). Motor activation in response to novel stressors and experimentally elevated levels of transcription factors in the striatum correlate well with rapid acquisition of 'low dose' cocaine self-administration behavior (Piazza et al, 2000;Mantsch et al, 2001;Colby et al, 2003). Perhaps more pertinent to the acceleration of initial drug taking, even at higher doses, is the immediate activational effect of social stress (Tidey and Miczek 1997;Miczek and Mutschler, 1996).…”

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

“…With 1 h of access per day (short access or ShA), rate of drug intake is low and stable over time. In contrast, with 6 or more hours of access per day (long access or LgA), rate of drug intake gradually escalates above initial levels (Ahmed and Koob, 1998;Ahmed et al, 2000;Mantsch et al, 2001;Paterson and Markou, 2003;Walker et al, 2003;Ferrario et al, 2005;Liu et al, 2005;Perry et al, 2006). The intensity of drug intake escalation is influenced by both the unit dose and the daily duration of drug access (Mantsch et al, 2004;Wee et al, 2007).…”