Single intracerebroventricular injection of botulinum toxin type A produces slow onset and long-term memory impairment in rats.

It is generally believed that the cholinergic system plays an important role in normal cognitive functioning. Botulinum toxin is the most potent toxin of the peripheral cholinergic system and today it is used in the treatment of a variety of neurological disorders. However, it is surprising that its effect on cognitive processes has been investigated in only two publications. Short-term effects of the central application of botulinum toxin (BTX) type B have been associated with cognitive impairment in animals, while results with type A are ambiguous. In the present study, we have investigated the duration of memory impairment after an intracerebroventricular administration of BTX-A in rats. Two experiments were performed, lasting 12 and 5 months, respectively. In both experiments, the same dose of BTX-A was applied (2 U/kg) and the Morris water maze test was used in the assessment of memory performance. Results show that a single icv injection of a small dose of BTX-A significantly impairs the water maze performance. In both experiments, impairment was apparently of a slow onset and long lasting (up to 12 months). The length and pattern of attenuation suggest development of dementia-like deficits. In addition to providing a potentially new experimental model of memory impairment, these results question the idea of an intracranial application of BTX in the treatment of CNS disorders.