Behavioral responses during the initial exposures to a low dose of cocaine in late preweanling and adult rats

Abstract

Human drug experimentation begins during late childhood and early adolescence, a critical time in physical and CNS development, when the immature CNS is vulnerable to the long-term effects of psychoactive drugs. Few preclinical animal studies have investigated responses to such drugs in a developmental stage equivalent to late childhood of humans. We used a rodent model to examine behavioral responses of female Sprague-Dawley late preweanling and adult rats during acute and repeated exposures to a low dose of cocaine. Results show that after cocaine injection, preweanling rats (18-21 days old) have locomotor responses that differ from adults, but after postnatal day 22, the responses are indistinguishable from adults even though rats are still not weaned. Before day 22, locomotor effects of cocaine differ from those in adults in three ways: preweanlings are active for a longer time after cocaine injection at day 18; preweanling activity peaks more rapidly after subcutaneous administration; and after only three injections of cocaine, a tolerance-like pattern is seen in preweanlings whereas an emerging pattern of sensitization to cocaine is seen in adults. The behavioral patterns of this age group offer a preclinical model of the early effects of drugs of abuse.

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

“…Similar to what is seen with the D2 agonists, there is an increase as the animals approach 20-35 days of age and then a decrease to the adult values ( fig. 6 d) [Spear and Brake, 1983;Collins and Izenwasser, 2004;Caster et al, 2005Caster et al, , 2007Kirstein, 2005, 2007;Frantz et al, 2007;Badanich et al, 2008;Parylak et al, 2008;Smith and Morrell, 2008]. These data support a D2 over D1 predominance in locomotion and possibly mRNA at the time periods where we see negative rCBV responses to cocaine or MPH, indicating the functional predominance of the D2 effects.…”

Role of the D1 receptor for the dopamine agonist-induced one-trial behavioral sensitization of preweanling rats

“…For example, psychostimulant-induced behavioral sensitization appears to be weaker and less persistent in preweanling rats than adults (Smith and Morrell 2008; McDougall et al 2009a). Similar to adults, the multi-trial behavioral sensitization of preweanling rats is influenced by associative processes, because sensitized responding is more persistent if drug pretreatment and testing occur in the same environmental context (Wood et al 1998; Zavala et al 2000).…”

Effects of D2 or combined D1/D2 receptor antagonism on the methamphetamine-induced one-trial and multi-trial behavioral sensitization of preweanling rats

“…Most importantly, the sensitized responding of preweanling rats appears to be weaker and less persistent than in older animals (Smith and Morrell 2008; McDougall et al 2009b). As with adults, the multi-trial behavioral sensitization of preweanling rats is stronger if drug pretreatment and testing occur in the same environmental context (i.e., context-dependent sensitization) (Wood et al 1998; Zavala et al 2000).…”