Drug addiction is a chronic relapsing disorder driven by molecular changes that occur in the brain in response to habitual drug use. Drug exposure produces profound moleculary changes during dependence and withdrawal that ultimately underlie many aspects of the resulting behavioral dysfunction. In order to identify these novel molecular targets in the brain, it is important to recapitulate drug intake and dependence using animal models. Importantly, the mode of drug exposure has a dramatic impact on the neuronal signaling pathways activated by drugs of abuse .
The Buczynski Lab incorporates both contingent (self-administration) and non-contingent (forced exposure) drug intake to recapitulate the drug effects in rodent models [1-3]. Models of self-administration facilitate study of the rewarding effects of drug exposure as well as cognitive aspects of operant responding (Figure 1). Non-contingent drug exposure models can produce physical dependence and facilitate studies of the emotional changes that occur during withdrawal. The efficacy of potential therapeutic treatments can then be evaluated using these models. Ultimately, we aim to utilize drug exposure procedures to validate novel druggable targets and to facilitate treatment efficacy testing.
Figure 1. Schematic of rodent drug self-administration.
Buczynski MW, Polis IY, Parsons LH. The volitional nature of nicotine exposure differentially alters anandamide and oleoylethanolamide levels in the ventral tegmental area. (2013) Neuropsychopharmacology 38, 574-84).
Buczynski MW, Herman MA, Hsu KL, Natividad LA, Irimia C, Polis IY, Pugh H, Chang JW, Niphakis MJ, Cravatt BF, Roberto M, Parsons LH. Diacylglycerol lipase disinhibits VTA DA neurons during chronic nicotine exposure. PNAS 113, 1086-91 (2016).
Irimia C, Buczynski MW, Natividad LA, Laredo SA, Avalos N, Parsons LH. Dysregulated signaling in the infralimbic cortex contributes to increased impulsivity during protracted alcohol abstinence. (2017), J. Neurosci.