Effects of acetoxycycloheximide and anisomycin on approach and escape responses to hypothalamic stimulation

The effects of acetoxycycloheximide (AXM) (7 mg/kg) and anisomycin (ANI) (25 and 150 mg/kg) on approach and escape responses induced by hypothalamic stimulation were studied in a situation in which male Swiss mice could initiate a continuous brain stimulation train by pressing a lever at one end of a box (ON-lever) and terminate this stimulation train by pressing a lever at the other end of the box (OFF-lever). AXM and ANI induced a large decrease in ON-OFF responses regardless of the level of stimulation presented (a low level just above the stimulation threshold and a high level which was twice the low level). Correspondingly, a significant increase was observed in the mean time during which animals remained unstimulated (NST) whereas mean time during which animals remained stimulated (ST) increased only slightly. The relative NST increase after treatment was always greater than the relative ST increase either at sites where before treatment NST was greater than ST or at sites where NST was shorter than ST. However, the animals in this latter electrode placement group (ST greater than NST) continued to shuttle and to make lever-pressing responses on the ON-lever, whereas the animals in the other placement group (ST less than NST) did not. These results are discussed in terms of possible interactions between disruptions of reinforcing systems induced by protein inhibitors and their effects on memory.