Preexposure to amphetamine and nicotine predisposes rats to self-administer a low dose of cocaine

Abstract

The acquisition of low-dose (0.25 mg/kg/infusion) intravenous cocaine self-administration was measured in rats that had received nine daily injections of amphetamine (1.0 mg/kg, IP), nicotine (0.6 mg/kg base weight, SC) or vehicle. For control rats, the acquisition of self-administration was gradual with the number of responses per 2 h daily test session increasing between days 3 and 9. By comparison, rats preexposed with amphetamine and nicotine demonstrated elevated response means during the early days of testing, suggesting more rapid acquisition. All groups eventually reached similar asymptotic levels of responding. The enhanced responding observed during the early days of testing in the rats preexposed with amphetamine and nicotine was due to an increased number of subjects that reliably self-administered cocaine. Thus, the rats preexposed with amphetamine and nicotine seemed predisposed to the reinforcing effects of cocaine. In contrast to the self-administration data, preexposure to nicotine failed to sensitize rats to the locomotor activating effects of cocaine. In fact, the same preexposure regimen appeared to produce tolerance to this effect of cocaine. These data give evidence that different mechanisms may mediate sensitization to the reinforcing and locomotor activating effects of cocaine.

Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

“…Animal studies clearly show that pre-exposure to psychomotor stimulants enhances subsequent SA of such drugs (Horger et al 1990(Horger et al , 1991(Horger et al , 1992Pierre and Vezina 1997;Vezina et al 1999;Lorrain et al 2000). Consistent with pre-exposure to nicotine (Horger et al 1992), and low-dose exposure to amphetamine (Pierre and Vezina 1997) we found a differential effect of low-dose MP preexposure on the reinforcing and locomotor activating effects of cocaine.…”

“…Animal studies have also shown that repeated exposure to psychostimulants increases the likelihood that rats will acquire drug self-administration (SA) with shorter latencies (Horger et al 1992) and at lower doses (Horger et al 1990), perhaps a more relevant display of sensitization as it relates to addiction. Pretreatment with such stimulants as nicotine, caffeine, and amphetamine produces enduring enhancements in the acquisition of cocaine SA (Valdez and Schenk 1994;Schenk and Davidson 1998).…”

“…Unfortunately, animal studies have provided conflicting answers (Laviola et al 1995;Ujike et al 1995;Snyder et al 1998;Wood et al 1998;Izenwasser et al 1999;McDougall et al 1999;Zavala et al 2000). Sensitization to MP in rodent models has been well documented (Shuster et al 1982;Gaytan et al 1997;Crawford et al 1998; but see McNamara et al 1993), but the use of relatively high doses in most studies, and the apparent inability of MP to induce long-term locomotor sensitization in young animals (McDougall et al 1999), has raised questions regarding the clinical relevance of such findings (National Institute of Mental Health 1999).Animal studies have also shown that repeated exposure to psychostimulants increases the likelihood that rats will acquire drug self-administration (SA) with shorter latencies (Horger et al 1992) and at lower doses (Horger et al 1990), perhaps a more relevant display of sensitization as it relates to addiction. Pretreatment with such stimulants as nicotine, caffeine, and amphetamine produces enduring enhancements in the acquisition of cocaine SA (Valdez and Schenk 1994;Schenk and Davidson 1998).…”

Rapid and Persistent Sensitization to the Reinforcing Effects of Cocaine

“…For example, self-administration of cocaine produces sensitization to the locomotor-activating effects (Hooks et al, 1994;Phillips and Di Ciano, 1996;Zapata et al, 2003;Ben-Shahar et al, 2004). It has also been demonstrated that rats receiving experimenter-administered stimulants, which produces a sensitized locomotor response, acquire selfadministration faster and/or at lower doses (Horger et al, 1990(Horger et al, , 1992Schenk et al, 1991). Animals treated this way also respond to higher breakpoints when subsequently tested on a PR schedule (Mendrek et al, 1998;Lorrain et al, 2000;Covington and Miczek, 2001;Suto et al, 2002Suto et al, , 2003Vezina et al, 2002).…”

Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice

“…This period of life is a very sensitive age in which the negative affective state associated with nicotine withdrawal is reduced while the rewarding action of nicotine is enhanced compared to adults (Carcoba et al, 2014;Dickson et al, 2014;Dickson et al, 2011;Hutchison and Riley, 2008;Lee et al, 2015;McQuown et al, 2009;Natividad et al, 2012;Natividad et al, 2010;Natividad et al, 2013;O'Dell et al, 2004;O'Dell et al, 2006;O'Dell et al, 2007;Shram et al, 2008;Torres et al, 2008;Wilmouth and Spear, 2004), making adolescents a vulnerable target to nicotine use and abuse as well as for use of other addictive drugs during adulthood. Consistent with this notion, previous studies have shown that nicotine exposure during adolescence can prime the use and abuse of cocaine, alcohol, and other addictive substances (Bechtholt and Mark, 2002;DiFranza and Guerrera, 1990;Horger et al, 1992;Hutchison and Riley, 2008;Kandel and Kandel, 2015;Kandel and Kandel, 2014;Kelley and Rowan, 2004;Kouri et al, 2001;Levine et al, 2011;Li et al, 2014;McQuown et al, 2007;McQuown et al, 2009;Meliska et al, 1995;Natividad et al, 2010;Rinker et al, 2011;Rosenberg, 2014;Schindler et al, 2012;Schneider et al, 2012). There is also evidence showing that about 90% of regular smokers start using tobacco at an early age, and that early onset smoking carries a major risk for the development of addiction to other drugs of abuse (Rimm et al, 1995).…”