Systemic carbachol used in radiation-controlled focal brain pharmacology can decrease rat running.
Radiation-controlled focal brain pharmacology is a method to concentrate a neuropharmacologic agent in any selected portion of the brain by irradiating that selected area and thereby lowering the BBB in that area. Then, when a drug that does not cross the normal BBB is administered systemically, the drug will preferentially penetrate and act only in the selected part of the brain. Rats received 20 Gy to the brainstem and then were tested with normal 0.9% saline 1 ml/kg, GABA 400 mg/kg, taurine 200 mg/kg, carbachol 1 mg/kg, amphetamine 2 mg/kg, and bicuculline methiodide 27 mg/kg. Opening the BBB produced no change in the average amount of running following the injection of saline. With the BBB closed, carbachol, bicuculline methiodide and taurine produced no statistically significant effect compared to saline. Comparing the effects of a drug when the BBB is open to that of saline when the BBB is open showed no significant effect of bicuculline methiodide, taurine and GABA. Carbachol produced a 73% reduction, significant at p less than .0001. Comparing a drug when the BBB is open to the same drug when the BBB is closed showed no significant effect of bicuculline methiodide, taurine and GABA. Carbachol produced a 65% reduction, significant at p less than .001. This shows that radiation-controlled focal brain pharmacology with carbachol can decrease the complex behavior of running.