NMDA-GABA interactions in an animal model of behaviour: a gating mechanism from motivation toward psychotic-like symptoms.
We studied the effects of desipramine, alprazolam, muscimol and dizocilpine (MK-801) (alone or associated with desipramine) in the forced swimming test in rats after long-lasting termination of chronic exposure to vehicle and pentylenetetrazol. Sensitisation with pentylenetetrazol was ineffective in changing immobility time in the forced swimming test compared to vehicle treatment; pentylenetetrazol enhanced the anti-immobility effect of desipramine, abolished the anti-immobility effect of alprazolam and did not affect the anti-immobility effect of muscimol. MK-801 at the dose that did not modify immobility time in vehicle-treated rats and in pentylenetetrazol-treated animals strongly potentiated the anti-immobility effect of desipramine in pentylenetetrazol-treated rats. MK-801 in association with desipramine induced a marked hyperlocomotion and hyperexcitability, with swaying movements and oral stereotypies in pentylenetetrazol-sensitised rats. Results are considered the experimental representation of a 'gating mechanism' toward psychotic-like symptoms.
Sabatino
M
M
Institute of Human Physiology, Faculty of Medicine, Policlinico P. Giaccone, University of Palermo, Italy.
Cannizzaro
C
C
Flugy
A
A
Gagliand
M
M
Mineo
A
A
Cannizzaro
G
G
D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000502:physiology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D011618:Psychotic Disorders / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D003891:Desipramine; D010433:Pentylenetetrazole; D000525:Alprazolam