Altered dopamine D-1 and D-2 receptor mRNA expression in mesencephalon from mice exposed to repeated treatments with methamphetamine and cannabinoid CB1 agonist methanandamide

作者：Landa Leos; Jurajda Michal; Sulcova Alexandra^*

来源：Neuroendocrinology Letters, 2012, 33(4): 446-452.

• behavioural sensitization
• methamphetamine
• methanandamide
• D-1 and D-2 receptor mRNA expression
• mouse mesencephalon

OBJECTIVES: In our previous studies we found that both acute administration of CB1 receptor agonist methanandamide and repeated methanandamide pretreatment prior to methamphetamine challenge dose elicited increase in the CB1 receptor mRNA expression in the mouse mesencephalon. As a reciprocal cross-talk is reported between the cannabinoid CB1 and dopamine receptors, that are highly co-localized on brain neurones, we targeted possible changes in relative expression of dopamine D-1 and D-2 receptor mRNA in mesencephalon in mice sensitized by repeated treatments to methamphetamine stimulatory effects and cross-sensitized to methamphetamine by cannabinoid CB1 receptor agonist methanandamide pre-treatment. %26lt;br%26gt;METHODS: To confirm development of behavioural sensitization or cross-sensitization, respectively, we observed changes in locomotion using the open field test. Mice were treated repeatedly with either methamphetamine or methamphetamine after repeated pre-treatment with methanandamide. After each measurement of locomotion one third of animals were sacrificed and the brain was stored. RNA was isolated from the midbrain and used for reverse transcription and subsequent real-time PCR. RESULTS AND %26lt;br%26gt;CONCLUSION: As in many of our earlier studies with the same dosage regimen we found in the behavioural part both development of sensitization to methamphetamine stimulatory effects after repeated treatment and cross-sensitization to them by pre-treatment with cannabinoid receptor CB1 agonist methanandamide. Real-time PCR analyses showed an increase in D-1 receptor mRNA expression after the first dose of methamphetamine (that persisted also after the last dose of methamphetamine) and after the first dose of methanandamide (which also persisted after the methamphetamine challenge dose). In opposite a significant decrease in D-2 receptor mRNA expression both after the first dose of methamphetamine and methanandamide (that persisted also after the methamphetamine challenge doses) was registered. Thus, our results suggest that both methamphetmine and methanandamide treatment can provoke changes in dopamine receptor density in mouse mesenpcephalon, the increase in D-1 and decrease in D-2 receptor subtypes.

• 出版日期2012