| Title |
Enhancement of social novelty discrimination by positive allosteric modulators at metabotropic glutamate 5 receptors: adolescent administration prevents adult-onset deficits induced by neonatal treatment with phencyclidine
|
|---|---|
| Published in |
Psychopharmacology, September 2012
|
| DOI | 10.1007/s00213-012-2845-3 |
| Pubmed ID | |
| Authors |
Nicholas E. Clifton, Nadège Morisot, Sylvie Girardon, Mark J. Millan, Florence Loiseau |
| Abstract |
Metabotropic glutamate-5 receptors (mGluR5), which physically and functionally interact with N-methyl-D-Aspartate (NMDA) receptors, likewise control cognitive processes and have been proposed as targets for novel classes of antipsychotic agent. Since social cognition is impaired in schizophrenia and disrupted by NMDA receptor antagonists like dizocilpine, we evaluated its potential modulation by mGluR5. Acute administration (0.63-40 mg/kg) of the mGluR5 positive allosteric modulators (PAMs), 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and ADX47273, reversed a delay-induced impairment in social novelty discrimination (SND) in adult rats. The action of CDPPB was blocked by the mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (2.5-10 mg/kg), and was also expressed upon microinjection into frontal cortex (0.63-10 μg/side), but not striatum. Supporting an interrelationship between mGluR5 and NMDA receptors, enhancement of SND by CDPPB was blocked by dizocilpine (0.08 mg/kg) while, reciprocally, dizocilpine-induced impairment in SND was attenuated by CDPPB (10 mg/kg). The SND deficit elicited by post-natal administration of phencyclidine (10 mg/kg, days 7-11) was reversed by CDPPB or ADX47273 in adults at week 8. This phencyclidine-induced impairment in cognition emerged in adult rats from week 7 on, and chronic, pre-symptomatic treatment of adolescent rats with CDPPB over weeks 5-6 (10 mg/kg per day) prevented the appearance of SND deficits in adults until at least week 13. In conclusion, as evaluated by a SND procedure, mGluR5 PAMs promote social cognition via actions expressed in interaction with NMDA receptors and exerted in frontal cortex. MGluR5 PAMs not only reverse but also (when given during adolescence) prevent the emergence of cognitive impairment associated with a developmental model of schizophrenia. |
Mendeley readers
The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 3% |
| Unknown | 59 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 13 | 21% |
| Researcher | 10 | 16% |
| Student > Ph. D. Student | 8 | 13% |
| Student > Bachelor | 6 | 10% |
| Student > Doctoral Student | 3 | 5% |
| Other | 9 | 15% |
| Unknown | 12 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Psychology | 13 | 21% |
| Agricultural and Biological Sciences | 7 | 11% |
| Medicine and Dentistry | 7 | 11% |
| Neuroscience | 6 | 10% |
| Biochemistry, Genetics and Molecular Biology | 5 | 8% |
| Other | 5 | 8% |
| Unknown | 18 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 October 2013.
All research outputs
#15,284,663
of 22,729,647 outputs
Outputs from Psychopharmacology
#4,238
of 5,337 outputs
Outputs of similar age
#95,582
of 152,103 outputs
Outputs of similar age from Psychopharmacology
#28
of 43 outputs
Altmetric has tracked 22,729,647 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,337 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 152,103 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.