While abuse and addiction to opiates has been a long-standing problem, the recent surge in abuse of opiate analgesics foreshadows the potential for rising rates of addiction to opiates. Repeated administration of drugs of abuse, such as morphine, causes a progressive and persistent sensitization of its locomotor stimulant and positive reinforcing effects. Sensitization to morphine can be sustained for several months after drug cessation and serves as a useful animal model of plasticity and the neuroadaptations associated with repeated administration of opioids having abuse potential. Studies show that sensitization has a close relationship with relapse, compulsive drug-seeking, and drug-taking behavior. Recent evidence suggests a role for the hippocampus in controlling these long-lasting behavioral adaptations. Investigation of an opiate-induced sensitization may help us to better understand the relapse mechanisms and provide new strategies for the treatment of drug addiction. Additionally, the key role of hippocampal synapses in learning and memory suggests that an understanding of the role of its specialized subcellular compartments in addictive processes is essential. Glutamatergic systems are thought to be involved in opiate-induced neuronal and behavioral plasticity although the mechanisms underlying these effects are only beginning to be understood. In our lab we analyze the role of synaptic AMPA glutamate receptors in the neuronal adaptations associated with repeated administration of morphine. More specifically, we study how morphine administration modulates synaptic transmission and plasticity at hippocampal synapses by altering the expression and composition of AMPA glutamate receptors, and how these adaptive effects will persist over time leading to neuroadaptions in glutamatergic synaptic function which could be responsible for the long-term behavioral sensitization induced by repeated morphine administration.
A second project in the lab is focused in elucidating the molecular mechanisms underlying morphine-induced pain sensitivity. It’s known that abrupt abstinence or withdrawal from opiate drugs causes a series of severe adverse symptoms, which keep drug-dependent individuals craving continued opiates. One of the core of withdrawal symptoms is an increase in pain sensitivity (pain sensitization or hyperalgesia). This pain sensitization is due to synaptic plasticity, particularly in the spinal cord and primary afferents. It has been demonstrated that AMPA glutamate receptor trafficking within the spinal cord is involved in the development of pain sensitivity. In our lab we analyze changes in AMPA receptor expression occurring in sensitivity at two different levels: 1) spinal cord and 2) primary afferent neurons. These studies are performed by combining behavioral paradigms with biochemical and state-of-art electrophysiological techniques.