THE EFFECTS OF INTRAACCUMBENS NEUROTENSIN ON SENSORIMOTOR GATING

Neurotensin is a neuropeptide which coexists with mesolimbic dopamine. Previous studies have shown that centrally administered neurotensin c an modulate the activity of mesolimbic dopamine with a profile similar to neuroleptics. For example, infusions of neurotensin into the nucle us accumbens inhibit amphetamine-induced hyperlocomotion. Prepulse inh ibition (PPI) occurs when a weak prestimulus ('prepulse') inhibits the amplitude of the startle response to an intense stimulus ('pulse'). P PI is an operational measure of sensorimotor gating which is strongly regulated by mesolimbic dopamine. This study examined the effects of v arious doses of neurotensin infused into the nucleus accumbens of rats on the prepulse inhibition (PPI) of their acoustic startle reflex. Ne urotensin (0.25-5.0 mu g) was infused into the nucleus accumbens of ra ts. Animals then received subcutaneous injections of amphetamine (2 mg /kg) or saline and were placed in startle chambers where measures of s tartle amplitude and PPI were obtained. Neurotensin increased baseline PPI and blocked amphetamine-induced disruption of PPI in a dose-depen dent fashion. The lowest dose of neurotensin tested (0.25 mu g) signif icantly increased baseline PPI and both 0.25 and 1.0 mu g neurotensin blocked amphetamine-induced decreases in PPI. The 5.0 mu g dose of neu rotensin had no significant effect on prepulse inhibition. Neurotensin had no effect on the amplitude of the acoustic startle reflex in amph etamine- or saline-treated rats. The results suggest that intra-accumb ens neurotensin has a significant, dose-dependent effect on sensorimot or gating in which lower doses (0.25-1.0 mu g) exhibit a neuroleptic-l ike action.