COGNITIVE IMPAIRMENT IN SPONTANEOUSLY HYPERTENSIVE RATS - ROLE OF CENTRAL NICOTINIC RECEPTORS .1.

Both human essential hypertension and genetically induced hypertension in rats have been associated with a range of impairments of cognitive ability. The spontaneous hypertensive rat (SHR) previously has been s hown to exhibit a decrease in the expression of brain nicotinic acetyl choline receptors, a factor that could play a role in the impaired abi lity of this strain in the performance of learning and memory-related tasks. The purpose of this study was to help determine whether task im pairment by SHR was related to the reduced expression of central nicot inic acetylcholine receptors, Twelve-week-old SHR were tested in two p hases of a water maze (spatial memory) task, and their performance was compared with that of two age-matched normotensive strains, Wistar Ky oto (WKY) and Wistar rats. During Phase 1, SHR exhibited significantly increased latencies to locate a hidden platform as compared with eith er WKY or Wistar rats. During Phase 2 (subsequent series of trials aft er a 4-day inter-phase period), where rats were required to find a new platform location, SHR again exhibited significantly impaired perform ance compared to the normotensive strains. In a single trial passive a voidance paradigm, SHR again displayed significantly reduced avoidance behavior as compared with both WKY and Wistar rats. In consecutive co ronal sections, the density of [H-3]cytisine binding sites was decreas ed in SHR by up to 25% in about half of the brain regions examined, wi th the deficits particularly apparent in cephalic regions. The binding of [I-125]alpha-bungarotoxin to brain sections also was decreased in SHR; however, only certain brain areas exhibited significant interstra in differences. These alterations in the expression of putative nicoti nic receptor subtypes in SHR were not due to changes in the density of cholinergic neurons since there were no interstrain differences in th e binding densities for [H-3]vesamicol, which labels the vesicular ace tylcholine transporter. Moreover, the magnitude of nicotine-stimulated rubidium efflux from cortical and striatal synaptosomes in vitro was significantly reduced in samples derived from SHR as compared with tho se from normotensive rats. These results are consistent with the possi bility that a reduction in the expression of cortical nicotinic recept ors in SHR plays a role in this strain's impaired performance of both spatial and non-spatial learning and memory-related tasks. (C) 1997 El sevier Science B.V.