Another factor to be considered is that all previous studies (see above) applied the TMS stimulus monolaterally, yet obtaining a reduction of alcohol craving (Mishra et al., 2010). While alcohol intake was not measured, and contralateral effects cannot be excluded a priori, it is possible that application of TMS bilaterally, as in the case of the H-coil (Feil and Zangen, 2010), would yield stronger cortical activation (larger number of fibers activated) with an increased probability of a significant increment of bilateral DA release. It should be noted that unilateral TMS application has already been reported to increase DA release (Strafella et al., 2001) omolaterally in the human striatum, as well as in rodents (Keck et al., 2002; Zangen and Hyodo, 2002), and even in morphine-withdrawn rats (Erhardt et al., 2004), thereby supporting the rationale outlined above. Although Strafella et al. (2001) proposed activation of (Glu-containing) cortico-fugal fibers making synaptic contact with DA-containing terminals in the ventral striatum, to explain their results, it should be noted that the existence of axo-axonic contacts has always being questioned based on the lack of appropriate anatomical observations (Groenewegen et al., 1991; Meredith et al., 2008).
