We examined whether acetylcholine release in the hippocampus and striatum and noradrenaline release in the hippocampus is altered in CB1 receptor-de®cient mice. The electrically evoked tritium over¯ow from hippocampal slices preincubated with [3 H]-choline was increased by about 100% in CB1 7/7 compared to CB1 +/+ mice whereas the electrically evoked tritium over¯ow from striatal slices preincubated with [3 H]-choline and from hippocampal slices preincubated with [3 H]- noradrenaline did not di€er. The cannabinoid receptor agonist, WIN 55,212-2, inhibited, and the CB1 receptor antagonist, SR 141716, facilitated, the evoked tritium over¯ow from hippocampal slices (preincubated with [3 H]-choline) from CB1 +/+ as opposed to...

Loss of cannabinoid receptors (CB1) occurs prior to neurodegeneration in Huntington’s disease (HD). The levels and distribution of CB1 RNA were equivalent in 3-week-old mice regardless of genotype demonstrating that the specific factors and appropriate chromatin structure that lead to the transcription of CB1 were present in the striatum of young R6/2 and R6/1 transgenic HD mice. The expression of the mutant HD transgene led progressively to decreased steadystate levels of CB1 mRNA in neurons of the lateral striatum, which was dependent on the size of the CAG repeat and relative expression of the gene encoding mutant huntingtin (HD). Although it is known that...

The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) has been used as an effective drug for treating dopamine depletion-induced Parkinson’s disease (PD). However, long-term administration of L-DOPA produces motor complications. L-DOPA has also been found to modify the two key signaling cascades, protein kinase A/dopamine- and cAMPregulated phosphoprotein of 32 kDa (DARPP-32) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), in striatal neurons, which are thought to play a pivotal role in forming motor complications. In the present study, we tested the possible effect of a CB1 cannabinoid receptor agonist on L-DOPA-stimulated abnormal behavioral and signaling responses in vivo. Intermittent L-DOPA administration for 3 weeks induced motor...