Sex differences in memory performance in the object recognition test. Possible role of histamine receptors

The mnemonic performances of male and female rats were compared in an object recognition test. Females were still able to recognize a previously identified object after a 90-min between-trial interval, compared with only 60 min in the males. Because histamine (HA) involvement in memory processes has been strongly suggested, the effect of H3-HA autoreceptor antagonist thioperamide was investigated. This drug was found to produce a dose-dependent promnestic effect in both sexes, but it did not influence the time course of memory retrieval. These behavioral data were compared to the density of H1-HA, H2-HA, and H3-HA receptors in cortical membranes. The densities of H1-HA and H2-HA receptors were greater in the females, whereas that of H3-HA was substantially the same in both sexes. The behavioral effect of thioperamide was very similar in both sexes, and this agrees with a similar H3-HA receptor density; however a better memory performance might have been expected in the female after thioperamide treatment (in view of different H1-HA and H2-HA receptor density), but this was not found. Because thioperamide has also been demonstrated to influence the acetylcholine release, its possible role in regulating the cholinergic memory effect was investigated. The scopolamine-reduced visual retrieval was antagonized by thioperamide in a similar way in both sexes. In conclusion, these data have shown a better performance of the female in a visual memory test, but this behavioral difference could not be affected by an H3-HA receptor-dependent manipulation of histaminergic and cholinergic systems.