Effects of amperozide, a putative antipsychotic drug, on rat midbrain dopamine neurons recorded in vivo.
The effect of the putative antipsychotic compound amperozide on the electrical activity of single identified midbrain dopamine (DA) neurons was investigated in the chloral hydrate anesthetized male rat. While the activity of DA cells in the substantia nigra was unaffected, DA neurons of the ventral tegmental area (VTA), the origin of the mesolimbocortical DA system, were affected in either of two ways: 1) increased firing rate and burst firing, i.e. an excitation, or 2) regularization of the firing pattern. Reversible cold inactivation of the medical prefrontal cortex (PFC) induced a pacemaker-like firing of VTA-DA cells, an effect blocked by amperozide in the cells excited by the drug. Cells responding with a regularization were not protected against the effect of PFC inactivation. These different effects of amperozide, which may in part be mediated by 5-HT2 receptor blockade, suggest an antipsychotic activity of amperozide, particularly in schizophrenia with negative symptoms.
Grenhoff
J
J
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Tung
C S
CS
Ugedo
L
L
Svensson
T H
TH
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010879:Piperazines; D011619:Psychotropic Drugs; C049058:amperozide; D004298:Dopamine