Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests.

Drugs that act to reduce glutamatergic neurotransmission such as NMDA receptor antagonists exert antidepressant-like effects in a variety of experimental paradigms, but their therapeutic application is limited by undesired side effects. In contrast, agents that reduce glutamatergic tone by blocking type I metabotropic glutamate receptors have been suggested to have more a favorable side-effect profile. The present study aimed to compare the effects of mGluR1 antagonist (EMQMCM; JNJ16567083, 3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate, 0.156-10 mg/kg) and mGluR5 antagonist (MTEP, [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine, 1.25-10 mg/kg) in two behavioral screening assays commonly used to assess antidepressant-like activity. In the modified forced swim test in rats, imipramine (used as a positive control) decreased immobility (MED 40 mg/kg) and increased the duration of escape-oriented (climbing and diving; MED 20 mg/kg) behaviors. Both EMQMCM and MTEP decreased the floating duration (MED 1.25 and 2.5 mg/kg) and increased the duration of mobile behaviors (paddling and swimming; MED 2.5 and 5 mg/kg). EMQMCM but not MTEP increased the duration of escape behaviors (climbing and diving; MED 1.25 mg/kg). In the mouse tail suspension test, EMQMCM (5 but not 2.5, 10 and 25 mg/kg), 2-methyl-6-(phenylethynyl)-pyridine (MPEP, 10 but not 1 mg/kg) and MTEP (MED 25 mg/kg) decreased immobility scores. For EMQMCM, the dose-effect relationship was biphasic. With the exception of EMQMCM (10 mg/kg), locomotor activity in mice was not affected by treatments. The present study therefore suggests that acute blockade of mGluR5 and also of mGluR1 exerts antidepressant-like effects in behavioral despair tests in rats and mice.

Colostrinin, a polypeptide isolated from early milk, facilitates learning and memory in rats.

Initial observations in humans indicated that colostrinin, a complex of polypeptides derived from the colostrum of sheep, facilitates cognitive functioning in patients with Alzheimer's disease. Its effect on learning and memory in more controlled settings as well as the specificity of these effects were, however, unknown. The present experiments evaluated the effects of colostrinin on spatial learning (Morris water maze) and incidental memory (habituation test) in male Wistar rats of two age groups. Colostrinin, at a dose of 4 microg/rat IP, facilitated acquisition of spatial learning of 13- (aged) but not 3-month-old (young) rats. At the same dose, it improved incidental learning in aged rats, while the dose of 20 microg/rat attenuated it. Colostrinin did not change locomotor activity of rats. Taken together, the present findings indicate that colostrinin may have some beneficial effects on cognitive functioning, particularly in aged subjects. Given the fact that colostrum is the first nutritive agent of neonates, it might be speculated that its peptides may facilitate the early postnatal development of the cerebral neurons and their plasticity.

Social transmission of flavored tea preferences: facilitation by a vasopressin analog and oxytocin.

Social transmission of information was tested in a procedure in which a rat (Observer) could demonstrate preference for a flavored tea as drinking solution that a con-specific (Demonstrator) had consumed just prior to a period of social interaction between the two animals. The cue in this procedure, probably olfactory in nature, was remembered for a relatively short period of time. It was prolonged when the Observers were treated with dresglycinamide[Arg8]-vasopressin (DGAVP) or oxytocin immediately after the encounter with the Demonstrator. DGAVP was effective after the injection of 15 micrograms.kg-1 but not of 1.5 ng.kg-1. Oxytocin induced the effect in doses ranging from 1.5 ng.kg-1 to 15 micrograms.kg-1. A dose of 0.15 ng.kg-1 was inactive. The influence of the peptides was cue specific. It is concluded that DGAVP and oxytocin facilitate social transmission of information, as previously found for social recognition.