STRIATAL PATCH COMPARTMENT LESIONS REDUCE HABITUAL BEHAVIOR
ABSTRACT TERRELL AVONTAE JENRETTE STRIATAL PATCH COMPARTMENT LESIONS REDUCE HABITUAL BEHAVIOR Under the direction of KRISTEN A. HORNER, Ph.D. America spends roughly 600 billion dollars annually on cost related to drug addiction. The majority of current drug addiction research focuses on the rewarding properties of drugs of abuse. The current rate of relapse suggest the need for a greater understanding of habitual drug seeking behavior. The striatum is essential to habit formation and reward association. The striatum is composed of the patch and matrix compartments, and previous studies have shown that enhanced activation of the patch compartment relative to the matrix compartment is related to inflexible behaviors, such as stereotypy. Habitual behaviors are also inflexible in nature, but whether enhanced activation of the patch compartment contributes to habitual behavior is not known. Our experiment analyzed the role of the patch compartment in habit formation, by using a targeted neurotoxin to ablate the neurons of the patch compartment prior to sucrose self-administration. Rats were bilaterally infused in the striatum with the neurotoxin dermorphin-saporin (DERM-SAP) to ablate the neurons of the patch compartment or unconjugated saporin (SAP, as a control) and allowed to recover for eight days. The rats were then trained to self-administer sucrose using a random interval paradigm proven to generate habitual sucrose consumption. We then associated sucrose consumption with a negative stimulus (LiCl). Subjects were reintroduced to the self-administration chamber and rats that continued to lever press, despite learning to associate sucrose with a negative stimulus, were considered to exhibit habitual behavior. Our data shows that DERM-SAP pretreatment reduced sucrose self-administration upon reintroduction to the self-administration chamber in animals that received LiCl treatment, indicating that habit formation was attenuated in these animals. DERM-SAP pretreatment also altered c-Fos levels in the sensorimotor cortex, prefrontal cortex, dorsal lateral striatum, and dorsal medial striatum. This data demonstrates that ablation of the patch compartment reduces habitual behavior by reducing activity in the habitual circuit and increasing activity in the goal directed circuit.
Jenrette, Terrell Avontae