Preclinical evidence indicates that inactivation of subthalamic nucleus (STN) may be effective for treating
cocaine addiction, and
therapies that target STN, e.g.
deep brain stimulation, are available indicating that this may have clinical promise. Here, we assessed the therapeutic potential of STN inactivation using a translationally relevant economic approach that quantitatively describes
drug-taking behavior, and tested these results with
drug-seeking tasks. Economic demand for
cocaine was assessed in rats (n = 11) using a within-session threshold procedure in which
cocaine price (responses/mg
cocaine) was sequentially increased throughout the session.
Cocaine demand was assessed in this manner immediately after bilateral microinfusions into STN of either vehicle (artificial cerebrospinal fluid) or the GABAA receptor agonist
muscimol. A separate group of animals (n = 8) was tested for changes in
cocaine seeking either during extinction or in response to
cocaine-associated cues.
Muscimol-induced inhibition of STN significantly attenuated
cocaine consumption at high prices,
drug seeking during extinction and cued reinstatement of
cocaine seeking. In contrast, STN inhibition did not reduce
cocaine consumption at low prices or locomotor activity. Thus, STN inactivation reduced economic demand for
cocaine and multiple measures of
drug seeking during extinction. In view of the association between economic demand and addiction severity in both rat and human, these results indicate that STN inactivation has substantial clinical potential for treatment of
cocaine addiction.