Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure

Abstract

Rationale Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure. Objectives Determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats. Methods Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions. Results Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline. Conclusions Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders).

Consequences of adolescent use of alcohol and other drugs: Studies using rodent models

“…Performance on an attentional set-shifting task revealed no performance deficits after adolescent cocaine exposure, with adolescent exposed rats conversely exhibiting more rapid shifts in performance on the set-shifting task than controls, perhaps due to alterations in attentional mechanisms; this effect was evident when exposed animals were tested in adulthood (P70) but not late adolescence (P56) (Black et al, 2006). These findings differ somewhat from those of Kantak et al, (2014) where both adolescent (P37–55) and adult (P77–95) rats were allowed to either self-administer cocaine or were given cocaine non-contingently, and tested >2 weeks later on a strategy set-shifting task and reversal. Adolescent cocaine exposure did not disrupt performance on the set-shifting task, although non-contingent (but not self-administered) cocaine during adolescence impaired reversal acquisition.…”

“…This lack of notable effects of adolescent cocaine exposure on “executive function”-type tasks that rely in part on circuitry involving the PFC contrast with compelling evidence for neural alterations in these regions, as discussed below. Indeed, Kantak and colleagues (2014) suggested that the immaturity of the PFC during adolescence may exert a protective effect against cognitive alterations from repeated cocaine exposure. Clearly, more studies in this area are warranted.…”

Age- and sex-dependent effects of methamphetamine on cognitive flexibility and 5-HT2C receptor localization in the orbitofrontal cortex of Sprague-Dawley rats

“…Adult-onset females with a history of METH self-administration committed fewer early errors than their counterparts. Interestingly, this is consistent with two studies that reported facilitation of operant strategy reversal in males exposed to amphetamine during adolescence (Hankosky et al, 2013) and in males that self-administered cocaine during adulthood (Kantak et al, 2014). Although the cause of this facilitation is not known, it is possible that adult-onset females did not learn the original strategy as well and subsequently shifted faster due to reduced proactive interference (Sherrill et al, 2013).…”

Cocaine self‐administration enhances excitatory responses of pyramidal neurons in the rat medial prefrontal cortex to human immunodeficiency virus‐1 Tat

“…Age may play a role in the cocaine/Tat‐mediated mPFC neuronal over‐excitation. Although adolescent and adult rats show comparable intakes of self‐administered cocaine (Kerstetter & Kantak, ), the consequences of self‐administered cocaine differentially affect performance on PFC‐mediated tasks (Harvey et al ., ; Kantak et al ., ). In addition to age differences, the adolescent rats in our prior study received a large single bolus of experimenter‐injected cocaine once daily for 5 days (Napier et al ., ); in the current study, rats were trained to self‐administer (self‐titrate) small doses of cocaine over a 2‐h operant session for 14 days in the presence of cocaine‐paired cues, and such differences may also have contributed to the disparity in neurophysiological consequences.…”