Repeated exposure to cocaine leads to a progressive and enduring augmentation of locomotor and stereotyped behaviors in rats, a phenomenon known as behavioral sensitization. The neuronal plasticity underlying behavioral sensitization results in the enhancement of the incentive motivational effects of cocaine. Thus, studies examining the mechanisms underlying behavioral sensitization could provide new insight into plasticity in the CNS that may help elucidate the mechanisms underlying the shift to compulsive drug use among human psychostimulant addicts and lead to the development of novel pharmacological treatments for these diseases. Neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF) have been linked to the initiation and expression of cocaine-induced behavioral sensitization. The goal of this grant application is 1) to assess the influence of acute and repeated injections of cocaine on the expression of NT-3 and BDNF in the neostriatum, core and shell of the nucleus accumbens; and ii) to assess the effect of antisense oligonucleotide suppression of TrkB and TrkC receptor expression in the neostriatum, core or shell of the nucleus accumbens on cocaine-induced behavioral sensitization.
