Thus, repeated a7 nAChR agonist administration has been shown to improve auditory gating, Morris water maze learning, classical eyeblink conditioning, WZ8040 inhibitory avoidance and novel object recognition. Importantly, repeated, but not acute, administration of the a7 nAChR agonist TC-5619 improves performance in the novel object recognition test, indicating an enhanced effect with repeated administration in this test. Furthermore, it has been shown that agonists of nAChRs can produce long-lasting cognitive effects that outlast the presence of the compounds in the body. Furthermore, -nicotine binding sites correlate with performance in the Morris water maze task several days after nicotine administration, suggesting that the prolonged effects were mediated by an increased number of nAChRs. Specifically for the a7 nAChR, it has been shown that the a7 nAChR agonist, AZD0328 enhances novel object recognition and increases – bungarotoxin binding in mice 4–48 hours after administration. In a related study AZD0328 enhanced performance in a delayed response task in monkeys with effects evident more than one month after administration of the compound. Taken together, these studies suggest that increased receptor numbers may underlie the sustained cognitive effects of nAChR agonists, although a direct correlation between a7 nAChR levels and cognitive performance has not been investigated. PAMs of the a7 nAChR increase the response to an agonist and are divided into two types depending on whether they also decrease desensitization of the receptor or not. Compared to agonists, there is much less data regarding the cognitive effects of a7 nAChR PAMs in animals, and no published clinical data. However, documented effects include improvements of pre-pulse inhibition and auditory gating as well as short- and long-term memory, resembling the behavioral effects of the agonists. Since PAMs do not activate the receptor per se, but modulate the effects of endogenous transmitters, they may enable more subtle regulation of a7 nAChR responses compared to agonists, but on the other hand, a lack of activation by the PAMs alone may hamper their effectiveness in patients with decreased levels of endogenous activation. It is thus not clear whether agonists or PAMs are preferable for clinical use, or whether there are qualitative differences between these types of compounds in vivo in terms of repeated administration. We have recently demonstrated a fundamental in vivo difference between agonists and PAMs in that acute or repeated administration of the former, but not the latter, increases -BTX binding sites in the rat brain, reflecting an increased number of a7 nAChRs. Given that upregulation of the a7 nAChR might underlie the enhanced procognitive effect seen with repeated administration of a7 nAChR agonists, as well as the long-lasting cognitive effects of these compounds, it is pertinent to examine whether a7 nAChR PAMs exhibit similar properties, since they do not induce upregulation of the receptor. Here we use a rat social discrimination test to examine whether the a7 nAChR agonist A-582941 or the a7 nAChR PAMs, AVL3288 or PNU-120596, has procognitive effects after acute or repeated administration, respectively, and whether such effects are long-lasting.