Intraseptal procaine abolishes hypothalamic stimulation-induced wheel-running and hippocampal theta field activity in rats.

Rats were implanted chronically with hippocampal recording electrodes, a microinfusion guide cannula aimed at the medial septal nucleus, and an electrode for electrical stimulation of the posterior hypothalamic nucleus (PH). PH stimulation elicited running in rats placed in a wheel and simultaneously occurring hippocampal theta field activity (HPC-theta). In the preprocaine (PRE) testing condition, a positive linear relationship was demonstrated among the intensity of electrical stimulation of the PH, wheel-running speed, and the peak frequency of HPC-theta. HPC-theta amplitude reached an asymptote at the lowest levels of electrical stimulation of the PH. Procaine hydrochloride (1.5 microliters, 20% solution), a local anesthetic, was then infused into the medial septal nucleus (MS). Five minutes after the infusion, PH stimulation no longer induced wheel-running behavior or HPC-theta, and the remaining irregular field activity was significantly reduced in amplitude. Fifteen minutes after the procaine infusion, PH stimulation still did not elicit HPC-theta or running behavior in the majority of animals but did evoke large-amplitude sharp-waves. Thirty minutes after the procaine infusion, PH stimulation again elicited HPC-theta and running behavior, but HPC-theta peak frequency and running speeds were both significantly reduced compared with PRE values. Forty-five minutes after the infusion, HPC-theta amplitude had recovered to PRE values, but HPC-theta frequency and running speeds elicited by PH stimulation were still significantly reduced. By 60 min after procaine administration, the amplitude and frequency of HPC-theta and the running speeds elicited by PH stimulation recovered to PRE values. Multiple regression analysis revealed that the recovery pattern of running behavior reflected the frequency rather than the amplitude of HPC-theta. Neither saline control infusions into the MS nor procaine infusions into the lateral septum and paraventricular thalamic nucleus affected HPC-theta or running behavior. These findings are consistent with the notion that both the locomotor activity and "movement-related" HPC-theta frequency induced by electrically stimulating the PH were attributable to ascending activation of a hypothalamo-septal pathway and not to activation of descending brainstem or peripheral motor systems.