It has been proposed that activation of metabotropic glutamate receptor subtype 2/3 (mGluR2/3) may induce both antipsychotic and anxiolytic effects. The aim of this study was to evaluate further the effect of the mGluR2/3 agonist, LY354740 [(+)-2-aminobicyclo(3.1.0)hexane-2,6-dicarboxylate monohydrate] in animal models relevant to both psychotic and cognitive impairment in schizophrenia. The elevated plus maze was used to select the doses for further experiments, LY354740 induced anxiolytic-like effects at doses of 3 and 10 mg/kg but not 1 mg/kg. At a dose of 10 mg/kg. LY354740 attenuated phencyclidine (PCP)-induced locomotor activity. Administered alone, it had no effect on horizontal activity, but at doses of 3 and 10 mg/kg, slightly decreased vertical activity (rearings). LY354740 (1-10 mg/kg intraperitoneally) affected neither prepulse inhibition in normal rats nor reversed the disruption of prepulse inhibition produced by PCP (2 mg/kg subcutaneously). Moreover, LY354740 (3-10 mg/kg) did not modify PCP-induced working memory deficits assessed in a spontaneous alternation task and had no effect on PCP-evoked amnesia in the passive avoidance test. LY354740 alone (3 and 10 mg/kg) induced working memory deficits, but had no effect on acquisition of passive avoidance. In conclusion, LY354740 was effective in models for anxiety and positive symptoms of schizophrenia but not in models for sensorimotor gating and cognitive impairment.

In the current study we compared the potency of the selective metabotropic glutamate receptor (mGluR1) antagonist A-841720 (7-Azepan-1-yl-4-dimethylamino-7H-9-thia-1,5,7-triaza-fluoren-8-one) in rodent models of pain with its effects in models of learning and memory, to obtain information regarding the therapeutic window of this compound. A-841720 significantly reduced formalin-induced behaviours and complete Freund's adjuvant (CFA)-induced tactile allodynia, starting at doses of 1 and 10 mg/kg, respectively. At the dose of 3 mg/kg, however, A-841720 significantly reduced the percentage of spontaneous alternations in a radial-maze task. In contextual-fear conditioning, A-841720, given at the dose of 10 mg/kg before acquisition, significantly reduced freezing behaviour tested 24 h later. In the same task, repeated treatment for 5 days did not reduce the impairing effect of the challenge dose, indicating a lack of tolerance development. In a passive-avoidance task, A-841720 at 10 mg/kg administered before acquisition, significantly reduced the latency to enter the dark box on the retention test. Given that complete Freund's adjuvant is a better measure of analgesia, these results indicate that the selective mGluR1 antagonist A-841720 has analgesic potential in a dose range at which it also produces memory impairments. This diminishes its therapeutic potential for the treatment of chronic pain.

Memantine and neramexane are noncompetitive NMDA receptor antagonists which have been investigated for their promising effects in aiding memory in people with dementia. Memantine is approved for the treatment of Alzheimer's disease, and neramexane is currently under development for this indication. Therefore, the present study provided a comparative assessment of the effects of equimolar doses of memantine and neramexane on spatial (hippocampus-dependent) memory. Adult male rats were given only 3 training trials to learn the location of a hidden platform in a water maze. In control (vehicle-injected) rats, this minimal amount of training produced intact short-term (15 min), but poor long-term (24 h), memory. Pre-training administration of memantine or neramexane produced a dose-dependent enhancement of long-term memory. Pharmacokinetic experiments with equimolar doses of both agents indicated that lower plasma levels of neramexane were more effective than memantine at enhancing memory. The effective doses of both agents in the current study produced plasma levels (and extrapolated brain CSF levels) within a range of activity at NMDA receptors and plasma levels seen in patients with Alzheimer's disease. These findings provide support for the use of neramexane as a pharmacological intervention in the treatment of dementia.

Agonistic behaviour between male cellar spiders (Pholcus phalangioides ) was investigated to test whether (1) size difference determines which male achieves access to the female, (2) males are able to monopolize access to the female until egg laying and whether (3) female resource value increases before egg laying because of last-male sperm precedence. We further investigated whether (4) there is variation in time and energy spent on courtship and copulation depending on the degree of sperm competition, i.e. with or without rival present. In three experimental settings we introduced two males of either different or similar sizes, or a single male to a female. The mating units were constantly video-observed until the females produced their first egg sac. Experience, ownership and female resource value in terms of body size was controlled. Our results show that larger males achieve almost exclusive access to females. Size symmetrical settings resulted in increased fighting activity and duration but dominance did not influence mating success. If copulations were disturbed by the rival male, copulations were terminated earlier in symmetrical settings compared with asymmetrical settings. In 94.8% of trials only one copulation took place, suggesting that the copulating male successfully monopolized access to the female. Males confronted with a rival copulated longer but courted significantly shorter than lone males. Although the last male to copulate sires 88% of the offspring in P. phalangioides, neither fighting nor courtship activity increased before the female laid a batch of eggs. This suggests that males have no indication of the timing of oviposition.