Effects of ketanserin on the discrimination of electrical stimulation of the dorsal raphé nucleus in rats.
The electrical stimulation of the dorsal raphé nucleus was used as a training cue in a discrimination paradigm. Sprague-Dawley rats were trained to discriminate between electrical stimulation (ES; 200 microA) of the dorsal raphé nucleus (DRN) and non-stimulation. This was accomplished by associating ES with intraperitoneal (i.p.) injection of lithium chloride (LiCl), following the session with electrical stimulation. This made the drinking of saccharin during ES aversive by conditioned taste aversion. Following training, rats decreased saccharin consumption in ES sessions. This discrimination was learned within three pairings of the ES with LiCl. Lowering the ES current to 50-100 microA resulted in levels of saccharin consumption similar to non-stimulation levels, whereas 150 microA showed a response intermediate between the stimulation response at 200 microA and non-stimulation. The discrimination of ES of the DRN (200 microA) was not affected by prior administration of the 5-HT2 antagonist ketanserin (1 or 2 mg/kg, i.p.), suggesting that activation of 5-HT2 receptors is not the primary discriminative cue generated by ES. However, the 5-HT2A/2C agonist DOI (0.25-0.5 mg/kg, i.p.), substituted for ES of the DRN, i.e. animals reduced saccharin consumption following DOI administration. This substitution of DOI for ES was antagonized by the administration of ketanserin (1 mg/kg, i.p.). These results suggest that ES of the DRN has properties that are similar to the activation of 5-HT2A/2C receptors by DOI. However, other stimuli such as activation of other 5-HT receptors are also involved, given that the discriminative cues of ES are not blocked by the 5-HT2A/2C antagonist ketanserin.
Mokler
D J
DJ
Department of Pharmacology, University of New England, College of Osteopathic Medicine, Biddeford, ME 04005, USA. dmokler@mailbox.une.edu
Abbruzzese
S
S
Trumble
V
V
Whitten
B
B
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D003463:Cues; D004192:Discrimination, Psychological / Q000187:drug effects*; D004558:Electric Stimulation; D005795:Generalization, Stimulus / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012439:Saccharin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology; D013649:Taste / Q000187:drug effects
D000662:Amphetamines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013549:Sweetening Agents; D007650:Ketanserin; D012439:Saccharin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine