(915.8) Inhibition of prelimbic cortical inputs to the patch compartment of striatum reduces habitual methamphetamine self-administration

Poster Board Number: B201

Kristen Ashley Horner (Mercer University School of Medicine), Vaishnavi Bavadekar (Mercer University School of Medicine), Ashitha Dama (Mercer University School of Medicine), Maahi Jain (Mercer University School of Medicine), Hyma Muchandi (Mercer University School of Medicine), Ashton Taylor (Mercer University School of Medicine), Jamin Ahn (Mercer University School of Medicine), David Christy (Mercer University School of Medicine)

An imbalance in activity between that patch and matrix compartments of striatum is thought to result in inflexible and repetitive behaviors, such as psychostimulant-induced stereotypy. Habitual drug abuse is also inflexible, suggesting that an imbalance in activity between the patch and matrix s may underlie addiction.  In addition, the patch system receives information regarding reward from regions such as the prelimbic cortex, which likely also contributes to the development of habitual drug use. However, whether enhanced activation of the patch compartment is related to habitual drug use is not known.   The current study examined the role of the patch compartment in the development of habitual methamphetamine (METH) use by inhibiting inputs from the prelimbic cortex, which projects specifically to the neurons of the patch compartment and carries information related to reward, emotion and motivation. Rats were bilaterally infused in the prelimbic cortex with the inhibitory designer receptor exclusively activated by designer drugs (DREADD) pAAV-CaMKIIa-hM4D(Gi)-mCherry-AAV5, or vehicle and allowed to recover for 6 weeks. The rats were then implanted with jugular catheters and trained to self-administer METH using a random interval paradigm known to generate habitual behaviors.  Following the acquisition of METH self-administration, rats were then trained to associate METH with a negative stimulus, by pairing METH with lithium chloride or saline, as a control.  Confirmation of lithium chloride-induced aversion to METH was determined using conditioned place aversion.  After the development of aversion to METH, animals were reintroduced to the operant chambers and given the opportunity to self-administer METH. Our data indicates that inhibition of prelimbic inputs to the patch compartment using inhibitory DREADDs reduced METH self-administration upon reintroduction to the operant chamber in animals that had developed an aversion to METH, indicating that habitual drug use may have been attenuated in these animals. Furthermore, these animals showed almost equal levels of activation in the patch and matrix compartments, while animals that continued to self-administer METH showed an enhanced activation of the patch compartment relative to the matrix compartment. These data suggest that activation of the patch compartment by prelimbic cortex may be necessary for the development of habitual METH self-administration.

Support or Funding Information

NIH grant DA045308 awarded to KAH