Our laboratory is interested in the biological basis of motivated behavior. Distributed neural circuits including the prefrontal cortex, the nucleus accumbens or nAc, the amygdala, and multiple brainstem nuclei including the ventral tegmental area or VTA, locus ceruleus and the raphé nuclei are involved in the perception of salient stimuli in the environment and the processing of rewarding or aversive emotional and behavioral states in response to those stimuli. Our laboratory investigates how early developmental events impact upon subsequent brain and behavioral development through actions within these circuits. We are particularly interested in how prenatal or adolescent exposure to drugs of abuse, both legal and illicit, may alter the liability for drug-seeking and consuming behaviors later in adolescence or adulthood. We employ several sets of methods to explore these phenomena.



While substance abuse neurobiologists employ many behavioral methods, four are commonly used to investigate the acute responses and chronic adaptations to drugs of abuse: self-administration, intracranial self-stimulation or ICSS; conditioned place-preference or CPP; and locomotor sensitization. Intracranial self-stimulation, or ICSS, is an operant behavioral paradigm in which animals are trained to perform a task to deliver direct electrical stimulation to brain reward circuitry. Pharmacological agents, particularly drugs with abuse potential, exert predictable effects on the rate and pattern of this operant response. We employ ICSS in mice that have been exposed to cocaine in utero to investigate developmental changes in the pharmacology of this reward-based behavior. We have also addressed this developmental question with non-contingent behavioral paradigms such as locomotor sensitization and CPP.

Single-cell patch clamp electrophysiology in the acute in vitro brain slice preparation is a powerful tool for pharmacological dissection of synaptic mechanisms underlying a variety of neuroadaptive processes. We employ this technique to address several questions, including: 1. whether in utero exposure to drugs of abuse alters the development of synaptic transmission in the ventral tegmental area, nucleus accumbens, and other elements of brain reward circuitry; 2. whether changes in short- and long-term LTP-like plasticity occur following such early developmental exposures; and 3. whether alterations in the pharmacology of dopaminergic, serotonergic or glutamatergic systems may explain some of these phenomena.