Trk: A Neuromodulator of Age-Specific Behavioral and Neurochemical Responses to Cocaine in Mice

Abstract

Responses to psychostimulants vary with age, but the molecular etiologies of these differences are largely unknown. The goal of the present research was to identify age-specific behavioral and molecular adaptations to cocaine and to elucidate the mechanisms involved therein. Postweanling, periadolescent, and adult male CD-1 mice were exposed to cocaine (20 mg/kg) for 7 d. The rewarding effects of cocaine were assessed, as were the response to a Trk antagonist and the regulation of dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP-32). Cocaine was rewarding in both periadolescent and adult mice using a conditioned place preference procedure. In contrast, postweanling mice failed to demonstrate significant cocaine-induced place preference. Because components of the neurotrophin system including brain-derived neurotrophic factor and TrkB are developmentally regulated, their role in the age-specific effects of cocaine was determined using the Trk receptor antagonist K252a. Postweanling mice that received K252a before daily cocaine showed a significant place preference to the cocaine-paired environment that was not seen in the absence of K252a. DARPP-32 protein levels were significantly upregulated in the lateral region of the caudate-putamen exclusively in postweanling mice after chronic cocaine. Daily pretreatment with K252a attenuated the induction of DARPP-32 in the postweanling striatum. These data indicate that Trk neurotransmission plays a role in age-specific behavioral and molecular responses to cocaine and concurrently modulates DARPP-32 levels.

Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat

“…Conversely, studies with adult rats have shown a conditioned place preference at the same dose of MDMA (Marona-Lewicka et al, 1996), which suggests a developmental transition from drug aversion to drug preference between adolescence and adulthood at this dose. Similarly, previous research with other psychostimulants (e.g., cocaine and amphetamine) indicate that rats have substantially different place conditioning scores with the same dose of psychostimulant depending on the stage of adolescence (Badanich et al, 2006; Izenwasser, 2005; Niculescu et al, 2008). …”

Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats

“…Further, differences in the levels of p-Thr 34 -DARPP-32 in the striatum of adult and young (PND24) mice both at baseline and following cocaine administration have been demonstrated (Niculescu et al, 2008). Thus, the regulation of DARPP-32 phosphorylation by psychostimulants appears to be age-dependent and may play an important role in the age-specific responses to these drugs.…”

Antidepressant‐like effects of fenofibrate in mice via the hippocampal brain‐derived neurotrophic factor signalling pathway

“…Chicken anti‐BDNF neutralizing antibody and chicken IgY control Ig were dissolved in ACSF. The dosages of fenofibrate (50, 100 mg·kg −1 ), fluoxetine (20 mg·kg −1 ), BrdU (75 mg·kg −1 ), K252a (50 ng per mouse), GW6471 (2 μg per mouse), rimonabant (30 μg per mouse), AM630 (10 μg per mouse) and anti‐BDNF neutralizing antibody (60 ng per mouse) were chosen based on previous reports (Niculescu et al, ; Hough et al, ; Fang et al, ; Jiang et al, , , ; Citraro et al, ; Barbiero et al, ). Fenofibrate, fluoxetine and BrdU were administered i.p.…”