Yohimbine disrupts prepulse inhibition in rats via action at 5-HT1A receptors, not alpha2-adrenoceptors.
BACKGROUND
Prepulse inhibition (PPI) of the acoustic startle response is an operational measure of sensorimotor gating that can be assessed in both humans and animals. The noradrenergic system appears to play a role in PPI as the alpha1 agonist cirazoline disrupts PPI and the alpha1 antagonist prazosin blocks the disruptions in PPI produced by phencyclidine.


OBJECTIVE
To better understand the role of adrenergic receptors in the modulation of PPI, we assessed the effects of the alpha2 adrenergic antagonist yohimbine (2.5, 5.0, and 7.5 mg/kg) on PPI.


RESULTS
Yohimbine reduced PPI at the 5.0 and 7.5 mg/kg doses, without significantly affecting startle magnitude. In separate experiments, we examined whether adrenergic or serotonergic compounds blocked this disruption in PPI produced by yohimbine. There was a trend for the alpha2 agonist clonidine (0.01, 0.02 mg/kg) to attenuate the PPI disruption produced by yohimbine. However, other alpha2 agonists (guanfacine, medetomidine) and an alpha1 antagonist (prazosin) failed to prevent the disruption. The alpha2 antagonist atipamezole weakly decreased PPI in a narrow dose range (0.3-1.0 mg/kg). The 5-HT1A antagonist WAY100,635 (0.1, 0.3 mg/kg) significantly prevented the yohimbine-induced disruption of PPI.


CONCLUSIONS
These findings indicate that (1) yohimbine disrupts PPI in rats and (2) the yohimbine-induced disruption of PPI is largely due to the 5-HT1A partial agonist properties of yohimbine.
Powell
Susan B
SB
Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA. sbpowell@ucsd.edu
Palomo
Javier
J
Carasso
Barbara S
BS
Bakshi
Vaishali P
VP
Geyer
Mark A
MA
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016316:Guanfacine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007267:Injections; D008297:Male; D020926:Medetomidine / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D010879:Piperazines; D011725:Pyridines; D018341:Receptors, Adrenergic, alpha-2; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; C050701:atipamezole; D044282:Receptor, Serotonin, 5-HT1A; D015016:Yohimbine; D016316:Guanfacine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D003000:Clonidine; D020926:Medetomidine; D011224:Prazosin
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