Behavioural and electroencephalographic effects of excitatory amino acid antagonists and sigma opiate/phencyclidine-like compounds in rats.
The present work was a comparative study of the electrocortical and behavioural effects of phencyclidine-like drugs and sigma-opiate drugs and of some excitatory amino acid antagonists. Phencyclidine-like drugs and sigma-opiate drugs elicited three dose-dependent electrocortical patterns: 1. Increase of periods of cortical desynchronization 2. Increase of the amplitude of fast (20-30 Hz) cortical waves; 3. Appearance of typical cortical complexes consisting of slow-wave (0.5-2 Hz) sharp-wave complexes. These effects were accompanied by excitatory motor symptoms, such as stereotyped movements of the neck and limbs. The NMDA competitive antagonist D,L-2-amino-5-phosphonovaleric acid (D,L-AP5), administered intracerebroventricularly (0.25-2 mumol), elicited phencyclidine-like stereotyped behaviour and cortical desynchronization, but failed to elicit/sigma typical cortical complexes. The non-selective amino acid antagonist cis-2,3 piperidine dicarboxilic acid (cis 2,3-PDA), administered intraperitoneally (3.3 mmol) failed to elicit both stereotyped behaviour and typical phencyclidine/sigma cortical complexes. The results strongly suggest the hypothesis that a reduction of excitatory amino acid neurotransmission, utilizing N-methyl-d-aspartate (NMDA)-preferring receptors, may be involved in the genesis of phencyclidine/sigma-induced stereotyped behaviour.
Sagratella
S
S
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Benedetti
M
M
Pézzola
A
A
Scotti de Carolis
A
A
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004569:Electroencephalography; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017480:Receptors, sigma; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D010875:Pipecolic Acids; D011957:Receptors, Opioid; D017480:Receptors, sigma; C029262:2,3-piperidinedicarboxylic acid; D015763:2-Amino-5-phosphonovalerate; D014633:Valine; D010622:Phencyclidine