CONICET | Buscador de Institutos y Recursos Humanos

Nicotine abuse is a public health problem of international scope, with enormous medical and socioeconomic consequences. Recent findings suggest that nicotine possesses similar neuroactive properties as the highly addictive psychomotor stimulants such as cocaine and amphetamine. Similar to these drugs of abuse, nicotine addiction is thought to be due to the activation of the mesocorticolimbic pathway. In abstinent drug addicts, the likelihood of relapse is high and limits the effectiveness of therapeutic interventions even after successful detoxification. Traditionally, the animal model of choice used to examine relapse to drug-seeking behavior has been the self-administration reinstatement procedure. However, place conditioning (PC) has been used to measure the rewarding as well as the aversive properties of drugs of abuse. The PC paradigm measures the incentive motivational properties of stimuli that become associated with drug effects through classical conditioning. The most favorable hypothesis at present suggests that the dependence to a psychoactive substance results of associative and adaptive processes in the mesocorticolimbic pathway, after repetitive exposure to the substance. It was suggested that these associative and adaptive mechanisms involve processes of learning and memory. This hypothesis implies the modification of the efficacy of numerous synapses, needing the action of transcription factors, synthesis of new proteins and transcription of the corresponding genes. We are trying to characterize some long-term mechanisms activated or repressed by nicotine after a CPP protocol. After the CPP, we study the transcription and the epigenetic factors. Our studies suggest that certain transcription factors participate after CPP, such as during reward and relapse, while during nicotine withdrawal epigenetic factors seem to play a more important role. Moreover, in nicotine reward and relapse groups, structures involved in memory consolidation are activated, suggesting that limbic structures modulate or participate in the establishment and maintenance of nicotine dependence.