title: 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.
authors.affiliation: Deparment of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Niculescu
authors.forename: Shane A
authors.initials: SA
authors.lastname: Perrine
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Miller
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Ehrlich
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Unterwald
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002227:Carbazoles / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000502:physiology; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology
chemical_list: D002227:Carbazoles; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D026121:Indole Alkaloids; C497929:Ppp1r1b protein, mouse; D017981:Receptors, Neurotransmitter; C049985:staurosporine aglycone; D020813:Receptor, trkB; D003042:Cocaine