Differential effects on learning by ventromedial vs lateral hypothalamic posttrial injection of substance P

The effects of post-trial injection of substance P (SP) into the lateral hypothalamus (LH) and the ventromedial hypothalamus (VMH) on passive avoidance learning was studied in rats. In the VMH, 50 ng and 500 ng SP influenced neither learning of a step-down avoidance nor of an alcove avoidance response. In contrast to these findings, 500 ng SP injected into the LH significantly enhanced retention of the alcove avoidance task. Similarly, in the step-down avoidance experiment, learning was strongly facilitated by posttrial injection of 50 ng as well as 500 ng SP into the LH. These results, together with our previous data showing amnesia with posttrial injection of SP into amygdala and substantia nigra, suggest that exogenously applied SP influences the activity of those brain regions shown to contain high densities of SP-positive nerve terminals. Interestingly, the effects of posttrial SP injection parallel the effects of post-trial electrical brain stimulation on passive avoidance learning. Hence, posttrial SP retroactively facilitates or impairs learning depending on where in the brain it is injected.