OBJECTIVES: In our previous studies we found that both acute administration of CB1 receptor agonist methanandamide and repeated methanandamide pre-treatment 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 D1 and D2 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. 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 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 D1 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 D2 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 D1 and decrease in D2 receptor subtypes.

• MeSH
• chování zvířat účinky léků   MeSH
• dopaminové látky farmakologie   MeSH
• interakce mezi receptory a ligandy účinky léků   MeSH
• kyseliny arachidonové farmakologie   MeSH
• lékové interakce MeSH
• messenger RNA analýza   MeSH
• methamfetamin farmakologie   MeSH
• mezencefalon účinky léků   metabolismus   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• náhodné rozdělení MeSH
• pohybová aktivita účinky léků   MeSH
• receptor kanabinoidní CB1 agonisté   MeSH
• receptory dopaminu D1 účinky léků   genetika   metabolismus   MeSH
• receptory dopaminu D2 účinky léků   genetika   metabolismus   MeSH
• rozvrh dávkování léků MeSH
• senzibilizace centrálního nervového systému účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Since among others also our previous studies suggested an interaction between the endocannabinoid system and methamphetamine brain mechanisms we focused on possible changes in relative expression of cannabinoid CB1 receptor mRNA in mesencephalon from mice sensitized by repeated treatments to methamphetamine stimulatory effects and cross-sensitized by cannabinoid CB1 receptor agonist methanandamide pre-treatment. METHODS: The Open Field Test was used to measure changes in terms of behavioural sensitization or cross-sensitization to drug effects on locomotion in male mice treated repeatedly with either methamphetamine or methamphetamine after pre-treatment with methanandamide. After each measurement 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 CONCLUSION: The evaluation of behavioural drug effects showed 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 revealed an increase in CB1 receptor mRNA expression after the first dose of methanandamide followed by decrease after the combined treatment with methamphetamine challenge dose. Our findings suggest that particularly repeated pre-treatment with CB1 agonist methanandamide can elicit increase in the mRNA expression level at least in the mouse mesencephalon neurons associated with cross-sensitization to methamphetamine stimulatory effects.

• MeSH
• adrenergní látky farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• kyseliny arachidonové farmakologie   MeSH
• lokomoce účinky léků   MeSH
• messenger RNA metabolismus   MeSH
• methamfetamin farmakologie   MeSH
• mezencefalon cytologie   účinky léků   metabolismus   MeSH
• myši MeSH
• náhodné rozdělení MeSH
• neurony účinky léků   metabolismus   MeSH
• receptor kanabinoidní CB1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH