Conditioning and place-specific sensitization of increases in activity induced by morphine in the VTA.

The conditionability of increases in locomotor activity induced by morphine administration into the ventral tegmental area was studied in rats. Morphine produced a clear increase in locomotor activity that was reversed by the opiate receptor blocker, naloxone, and blocked by the neuroleptic, pimozide, suggesting the mediation of this effect by the ascending mesolimbic dopamine system. The increase in locomotor activity showed sensitization with repeated morphine administrations and this sensitization was found to be specific to the environment in which morphine was administered. Conditioning tests also revealed that, in the absence of morphine, increased locomotor activity was elicited by the administration environment. Pimozide blocked the development of the conditioned sensitization. These data demonstrate that a learned association developed between this excitatory action of morphine and the administration environment. These results have important implications for the role of conditioning factors in relapse to drug use and may provide an explanation for conditioning data obtained when morphine is administered systemically.