Methamphetamine promotes habitual action and alters the density of striatal glutamate receptor and vesicular proteins in dorsal striatum

Addict Biol. 2018 May;23(3):857-867. doi: 10.1111/adb.12534. Epub 2017 Jul 14.

Abstract

Goal-directed actions are controlled by the value of the consequences they produce and so increase when what they produce is valuable and decrease when it is not. With continued invariant practice, however, goal-directed actions can become habits, controlled not by their consequences but by antecedent, reward-related states and stimuli. Here, we show that pre-exposure to methamphetamine (METH) caused abnormally rapid development of habitual control. Furthermore, these drug-induced habits differed strikingly from conventional habits; we found that they were insensitive both to changes in reward value and to the effects of negative feedback. In addition to these behavioral changes, METH exposure produced bidirectional changes to synaptic proteins in the dorsal striatum. In the dorsomedial striatum, a structure critical for goal-directed action, METH exposure was associated with a reduction in glutamate receptor and glutamate vesicular proteins, whereas in the dorsolateral striatum, a region that has previously been implicated in habit learning, there was an increase in these proteins. Together, these results indicate that METH exposure promotes habitual control of action that appears to be the result of bidirectional changes in glutamatergic transmission in the circuits underlying goal-directed and habit-based learning.

Keywords: dorsolateral striatum; dorsomedial striatum; glutamate; goal-directed; habits; methamphetamine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Central Nervous System Stimulants / pharmacology*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Formative Feedback
  • Habits
  • Male
  • Methamphetamine / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism
  • Receptors, Glutamate / drug effects*
  • Receptors, Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Reward
  • Vesicular Glutamate Transport Protein 1 / drug effects*
  • Vesicular Glutamate Transport Protein 1 / metabolism
  • Vesicular Glutamate Transport Protein 2 / drug effects*
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Central Nervous System Stimulants
  • NR1 NMDA receptor
  • NR2B NMDA receptor
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Slc17a6 protein, rat
  • Slc17a7 protein, rat
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Glutamate Transport Protein 2
  • Methamphetamine
  • glutamate receptor ionotropic, AMPA 2
  • N-methyl D-aspartate receptor subtype 2A