The effects of lesions of the habenular nuclei on the development of sensitization to the behavioral activational effects of repeatedly administered morphine in the rat.

The effects of lesions of the habenular nuclei on the development of sensitization to the behavioral activational effects of morphine (MOR), administered repeatedly either systemically or directly into the ventral tegmental area (VTA) were examined. Lesions of the habenular nuclei blocked the early-appearing sedative effects and enhanced the later-appearing locomotor activational effects seen after systemic injections of MOR (10 mg/kg, i.p.). Habenular lesions did not potentiate the development of sensitization to the locomotor-activational effects seen with the repeated, systemic administration of MOR. The bilateral injection of MOR (5.0 micrograms/0.5 microliter/side) directly into the VTA of animals with habenular lesions resulted in the performance of stereotyped behaviors that appeared as early as the second MOR exposure and remained at high levels with repeated MOR treatment. The stereotyped behavior shown by lesioned animals did not appear to interfere with the acute locomotor activational effects of intra-VTA MOR nor the development of sensitization to these effects when it was administered repeatedly. These results are in agreement with previous research suggesting that by disinhibiting the dopamine (DA) systems, habenular lesions enhance the acute behavioral activational effects of MOR. The results also suggest that the habenular nuclei do not control the changes in the response of the DA systems underlying the development of sensitization to the locomotor-activating effects of MOR when administered repeatedly.