45 A hallmark of Parkinson's disease (PD) is diminished dopaminergic 46 signaling in the striatum (caudate putamen, CPu), which leads to 47 increased release of acetylcholine (ACh) by disinhibited tonically 48 active interneurons with the consequence of a disturbed network 49 function and consecutive motor dysfunction. Current therapeutic 50 strategies are based on two major approaches in order to correct the 51 disturbed circuits of involuntary movement control, ie stimulation of 52 dopamine (DA) receptors on GABAergic medium spiny neurons and 53 inhibition of hypercholinergic activity of tonically active interneurons 54 (Day et al., 2006; Obeso et al., 2008). However, both approaches are 55 compromised by adverse side effects due to systemic drug application 56 (Whitney, 2007). In the pre-L-DOPA era, the first drugs that turned 57 out to have clinically significant anti-Parkinson activity were anti-58 cholinergics such as atropine and atropine-like derivatives (Duvoisin, 59 1967; Kaplan et al., 1954; Ordenstein, 1868). Today some of these 60 compounds are still commonly used in clinical practice, eg the 61 piperidine derivative Biperiden (Akineton®). Also, the PD-like side 62 effects of anti-psychotics are typically treated with anti-cholinergic 63 drugs, especially in younger patients (Ekdawi and Fowke, 1966; 64 Mamo et al., 1999). However, the most serious problem with these 65 systemically administered anti-cholinergics remains the occurrence 66 of well-known troublesome peripheral and central side effects, such 67 as mydriasis, paresis of accommodation (blurred vision), reduced 68 salivation (dry mouth), parotitis, dry eyes, muscular pain, loss of 69 power, alteration of voice, dysphagia, regurgitation, constipation, 70 urinary retention, prostatism, tachycardia, fever in warm weather, 71 hallucinations, memory problems and confusion. To avoid this 72 disadvantage we tested local anti-cholinergic treatment applying 73 botulinum neurotoxin A (BoNT-A) into the CPu of hemiparkinsonian 74 (hemi-PD) rats, a well established 6-hydroxydopamine (6-OHDA)-75 induced animal model of PD (Meredith et al., 2008). In this model, it 76 has been shown that intraperitoneally applied atropine antagonizes 77 the profound PD-typical akinesia (Schallert et al., 1978). In combina-78 tion with L-DOPA it supported the alleviation of excessive bracing 79 reactions and suppressed pathological circling of the PD rats (Schallert 80 et al., 1979). In our study, intrastriatal application of BoNT-A caused 81 complete long-term abolition of pathological apomorphine-induced