Adolescent rats are protected from the conditioned aversive properties of cocaine and lithium chloride

Abstract

In humans, most drug use is initiated during adolescence and adolescent users are more likely to become drug-dependent than adult users. Repeated, high levels of use are required for the transition from use to addiction. Individual levels of drug use are thought to result from a balance between the pleasant or rewarding and the unpleasant or aversive properties of the drug. Repeated high levels of drug use are required for the transition from drug use to dependence. We hypothesized that diminished aversive effects of drugs of abuse during adolescence might be one reason for higher rates of use and addiction during this phase. We therefore tested adolescent and adult CD rats in single-dose cocaine conditioned taste aversion (CTA) at a range of doses (10-40 mg/kg), and examined whether various behavioral markers of addiction vulnerability were correlated to outcome in cocaine CTA. We found that adolescents are indeed less susceptible to cocaine CTA. In fact, age was the predominant predictor of CTA outcome, predominating over measures of novelty-seeking, anxiety, and stress hormone levels, which are all known to be related to drug intake in other models. Furthermore, we found that adolescent rats are also less susceptible to conditioned taste aversion to a low dose of a non-addictive substance, lithium chloride. These results suggest that one explanation for elevated drug use and addiction among adolescents is reduced aversive or use-limiting effects of the drugs. This contributes to our understanding of why adolescence is a particularly vulnerable period for development of drug abuse.

Transient D1Dopamine Receptor Expression on Prefrontal Cortex Projection Neurons: Relationship to Enhanced Motivational Salience of Drug Cues in Adolescence

“…Comparatively, adolescents (P44) formed a strong preference for a context paired with the lowest (10 mg/kg) dose of cocaine used, corroborating findings from Schramm-Sapyta et al (2006). This is consistent with the notion that adolescence is characterized by a high sensitivity to reward (Chambers et al, 2003;Tirelli et al, 2003;Ernst et al, 2006), although this sensitivity may partly be caused by enhanced cortical drive as suggested here.…”

“…The assessment of motivational responsiveness to stimulants during development is not well defined in the literature for a number of reasons. Inconsistencies in paradigms used, handling stressors, ages, sex (Campbell et al, 2000), drug doses, and the use of stimulants with different behavioral sequelae, such as stereotypy, yield variable conclusions, ranging from decreased amphetamine place conditioning to a heightened sensitivity to cocaine place conditioning in adolescence (Campbell et al, 2000;Tirelli et al, 2003;Badanich et al, 2006;Balda et al, 2006;Schramm-Sapyta et al, 2006) (for review, see Brenhouse and Andersen, 2008). For example, handling is one such variable to consider.…”

Attenuated incubation of cocaine seeking in male rats trained to self-administer cocaine during periadolescence

“…However, not only is stimulus-reward learning intact after adolescent cocaine self-administration (Kerstetter and Kantak 2007), but also cocaine-induced devaluation of natural rewards is less affected by cocaine treatment in adolescence than adulthood (Schramm-Sapyta et al 2006). Additionally, sucrosestimulated dopamine efflux in the nucleus accumbens remains intact after cocaine treatment in adolescence but not in adulthood (Catlow and Kirstein 2007).…”

Inhibition of neuronal nitric oxide synthase prevents alterations in medial prefrontal cortex excitability induced by repeated cocaine administration

“…In total, 65 adolescent male Sprague-Dawley rats (5-6 weeks old; Spear 2000), age in which subjects are more vulnerable to develop drug addiction (Badanich et al 2006(Badanich et al , 2008Schramm-Sapyta et al 2006) were housed in group in a temperature-humidity-controlled vivarium under a 12-h light/dark cycle. Food and water were freely available.…”