Voluntary inhalation of methamphetamine: a novel strategy for studying intake non-invasively

C. Juarez-Portilla, R. D. Kim, M. Robotham, M. Tariq, M. Pitter, J. LeSauter, R. Silver

The abuse of the psychostimulant methamphetamine (MA) is associated with substantial costs and limited treatment options. To understand the mechanisms that lead to abuse, animal models of voluntary drug intake are crucial. We aimed to develop a protocol to study long-term non-invasive voluntary intake of MA in mice. Mice were maintained in their home cages and allowed daily 1 h access to an attached tunnel leading to a test chamber in which nebulized MA was available. Restated, if they went to the nebulizing chamber, they self-administered MA by inhalation. This protocol was compared to injected and to imposed exposure to nebulized MA, in a series of seven experiments. We established a concentration of nebulized MA at which motor activity increases following voluntary intake resembled that following MA injection and imposed inhalation. We found that mice regulated their exposure to MA, self-administering for shorter durations when concentrations of nebulized MA were increased. Mice acquire the available MA by repeatedly running in and out of the nebulizing chamber for brief bouts of intake. Such exposure to nebulized MA elevated plasma MA levels. There was limited evidence of sensitization of locomotor activity. Finally, blocking access to the wheel did not affect time spent in the nebulizing chamber. We conclude that administration of MA by nebulization is an effective route of self-administration, and our new protocol represents a promising tool for examining the transitions from first intake to long-term use and its behavioral and neural consequences in a non-invasive protocol.