Interactive effects of mGlu5 and 5-HT2A receptors on locomotor activity in mice.

Rationale: Metabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)(2A) activation, the interactions between serotonin 5-HT(2A) receptors and mGlu receptors may prove to be important for our understanding of these diseases.

Objective: We tested the effects of the serotonergic hallucinogen and 5-HT(2A) agonist, 2,5-dimethoxy-4-methylamphetamine (DOM), and the selective 5-HT(2A) antagonist, M100907, on locomotor activity in the mouse behavioral pattern monitor (BPM) in mGlu5 wild-type (WT) and knockout (KO) mice on a C57 background.

Isolation rearing of mice induces deficits in prepulse inhibition of the startle response.

Male 129T2 and C57BL/6J mice were housed either in groups of three (socials) or singly (isolates) at weaning. Six and seven weeks later, prepulse inhibition (PPI), startle reactivity, and locomotor activity (LMA) were measured. Isolation-reared mice of both strains exhibited PPI deficits compared to socially reared controls in at least one of the two PPI test sessions.

MDMA "ecstasy" alters hyperactive and perseverative behaviors in dopamine transporter knockout mice.

Rationale: Mice lacking the gene for the dopamine transporter (DAT) show a unique behavioral phenotype characterized by locomotor hyperactivity and repetitive circling in a novel environment. The hyperactivity of DAT (-/-) mice can be attenuated by psychostimulants and by serotonin uptake inhibitors, suggesting an important role for serotonin in the attenuation of locomotor hyperactivity in these mice.

Objectives: These studies characterized the effects of 3,4-methylenedioxy-N-methylamphetamine (MDMA), a serotonin releaser, on the amount and patterns of locomotor activity in DAT (+/+) and (-/-) mice.

The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice.

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice.

The mGluR5 antagonist MPEP, but not the mGluR2/3 agonist LY314582, augments PCP effects on prepulse inhibition and locomotor activity.

Phencyclidine (PCP), a non-competitive antagonist of ionotropic N-methyl-D-aspartate (NMDA) receptors, produces psychotomimetic effects, such as a disruption in prepulse inhibition (PPI) of the startle response. NMDA antagonists also induce locomotor hyperactivity in rodents. We hypothesized that, like NMDA receptors, metabotropic glutamate receptors (mGluRs) modulate PPI and locomotor activity either alone or, in the case of mGluR5, via interaction with NMDA receptors.