Chronic alcohol alters rewarded behaviors and striatal plasticity

Abstract

Chronic intermittent ethanol (CIE) alters neural functions and behaviors mediated by the dorsolateral striatum (DLS) and prefrontal cortex. Here, we examined the effects of prolonged (16-bout) CIE on DLS plasticity and DLS-mediated behaviors. Ex vivo electrophysiological recordings revealed loss in efficacy of DLS synaptically induced activation and absent long-term depression after CIE. CIE increased two-bottle choice drinking and impaired Pavlovian-to-instrumental transfer but not discriminated approach. These data suggest prolonged CIE impaired DLS plasticity, to produce associated changes in drinking and cue-controlled reward-seeking. Given recent evidence that less-prolonged CIE can promote certain dorsal striatal-mediated behaviors, CIE may drive chronicity-dependent adaptations in corticostriatal systems regulating behavior.

Keywords: Alcohol; dorsolateral striatum; reward.

Figure 1

Prolonged CIE impairs dorsal striatal synaptic plasticity. (a) Location of recordings made from synapses in DLS. (b) Population spike magnitude increased with stimulation amplitude, but CIE mice showed significantly lower values than air mice. (c) High-frequency stimulation (HFS) induced LTD in air, but not CIE, mice after each of three sets of trains compared with baseline. (d) Example traces. n = 6–8/group. Data are means ± SEM. *P < 0.05 versus air, #P < 0.05 versus baseline

Figure 2

Prolonged CIE impairs PIT and increases ethanol drinking. (a,b) CIE mice had significantly higher ethanol consumption and preference than air mice after the vapor chambers. (c) Air, but not CIE, mice pressed the active lever more in the presence of the CS+ than the CS− or during the intertrial interval (ITI), and both groups pressed the active lever more than the inactive lever regardless of CS. (d) Air and CIE mice made more head entries into the magazine in the presence of the CS+ than the CS− or during the ITI, although air mice made more head entries than CIE mice. n = 6–12/group. Data are means ± SEM. *P < 0.05 versus air, #P < 0.05 versus CS+