Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Abstract

The neural mechanisms responsible for the enhanced adolescent vulnerability for initiating drug abuse are unclear. We investigated whether age differences in dopamine neurotransmission could explain cocaine's enhanced psychomotor effects in the periadolescent rat. Electrical stimulation the medial forebrain bundle of anesthetized post-natal age 28 days (PN28) and PN65 rats elicited dopamine release in caudate nucleus and nucleus accumbens core before and after 15 mg/kg cocaine i.p. Extracellular dopamine concentrations were greater in PN65 than PN28 caudate following 20 and 60Hz stimulations and in the PN65 nucleus accumbens following 60Hz stimulations. Cocaine increased dopamine concentrations elicited by 20 Hz stimulations 3-fold in the adult, but almost 9-fold in periadolescent caudate. Dopamine release rate was lower in the periadolescent caudate although total dopamine clearance was similar to that of adults. The periadolescent caudate achieved adult levels of clearance by compensating for a lower V max with higher uptake affinity. Tighter regulation of extracellular dopamine by the higher uptake/release ratio in periadolescents led to greater increases after cocaine. In nucleus accumbens, dopamine release and V max were lower in periadolescents than adults, but uptake affinity and cocaine effects were similar. Immaturity of dopamine neurotransmission in dorsal striatum may underlie enhanced acute responses to psychostimulants in adolescent rats and suggests a mechanism for the greater vulnerability of adolescent humans to drug addiction.

Differential treatment regimen-related effects of cannabinoids on D1 and D2 receptors in adolescent and adult rat brain

“…Once adolescence is reached, synaptic elimination takes place and receptor density declines until reaching adult levels on PND 60 (Tarazi and Baldessarini, 2000). Fluctuations also take place in basal dopamine levels in the nucleus accumbens during adolescence (Badanich et al, 2006) and dopamine uptake/release ratios differ in the nucleus accumbens and caudate putamen in the adolescent and adult rodent brain (Walker and Kuhn, 2008). A similar profile of developmental overproduction in the dopamine system followed by synaptic elimination during late adolescence appears to take place in humans (reviewed by Spear, 2000;Weickert et al, 2007).…”

Emergence of sex differences in the development of substance use and abuse during adolescence

“…Dopaminergic innervation of dorsal, ventral striatum and prefrontal cortex reaches a peak during adolescence and then declines to adult levels in rodents and humans (Andersen & Gazzara, 1993, 1994, 1996; Haycock et al, 2003). Basal dopamine is lower in adolescent rat striatum, and studies of psychostimulant-induced changes in dopamine release are conflicting, with reports of responses both higher (for cocaine) and lower (for amphetamine) than are observed in adults (Camarini, Griffin, Yanke, Rosalina dos Santos, & Olive, 2008; Cao, Lotfipour, Loughlin, & Leslie, 2007; Kuczenski & Segal, 2002; Matthews, Bondi, Torres, & Moghaddam, 2013; Stansfield & Kirstein, 2005; Walker, Francis, Caster, & Kuhn, 2007; Walker et al, 2010). There is a hyperproduction of D1 and D2 receptors during adolescence followed by a pruning which could play a significant role in modulating dopamine function during adolescence (Andersen, Thompson, Rutstein, Hostetter, & Teicher, 2000; Meng, Ozawa, Itoh, & Takashima, 1999; Teicher, Andersen, & Hostetter, 1995).…”

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

“…It is perhaps relevant that DA release capacity increases from adolescence to adulthood, while the ratio of DA uptake to release declines (Walker and Kuhn 2008). These findings have lead Walker et al (2010) to suggest that age-dependent changes in DA release capacity may underlie some of the behavioral differences reported in adolescent and adult rats.…”