PT  - JOURNAL ARTICLE
AU  - Willins, David L.
AU  - Meltzer, Herbert Y.
TI  - Direct Injection of 5-HT<sub>2A</sub> Receptor Agonists into the Medial Prefrontal Cortex Produces a Head-Twitch Response in Rats
DP  - 1997 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 699--706
VI  - 282
IP  - 2
4099  - http://jpet.aspetjournals.org/content/282/2/699.short
4100  - http://jpet.aspetjournals.org/content/282/2/699.full
SO  - J Pharmacol Exp Ther1997 Aug 01; 282
AB  - The serotonin (5-HT)2A/2c agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT2C agonist 6-chloro-2-[1-piperazinyl]-pyrazine and the 5-HT2A partial agonist m-chloro-phenylpiperazine (mCPP) were injected bilaterally into the medial prefrontal cortex of male rats. DOI and mCPP, but not 6-chloro-2-[1-piperazinly]-pyrazine, elicited a dose-dependent head-twitch response (HTR). DOI-induced HTR had an ED50 of 12.8 nmoles/0.5 μl/side and was inhibited by the 5-HT2A antagonists ketanserin and MDL 100,907 but was not blocked by pretreatment with the selective 5-HT2C/2B antagonist SDZ SER 082. The HTR to mCPP demonstrated a bell-shaped dose-response curve with an ED50of 1.5 nmoles/0.5 μl/side and a peak effect after 3 nmoles/side. The response to mCPP was greatly diminished by both ketanserin and MDL 100,907 and was partially reversed by SDZ SER 082. These findings suggest that the HTR produced by the direct injection of serotonergic agonists into the medial prefrontal cortex is, in part, mediated by the activation of 5-HT2A receptors. Pretreatment of rats with the 5-HT1A agonist (±)-8-hydroxy-dipropylaminotetralin hydrobromide inhibited the HTR to DOI. This is consistent with other evidence that suggests a functional antagonism between 5-HT1A and 5-HT2A receptor activation. The HTR to DOI was potentiated by the novel 5-HT1A selective antagonist WAY 100,635, which suggests that 5-HT1Areceptors tonically regulate this behavioral response to stimulation of cortical 5-HT2A receptors. The American Society for Pharmacology and Experimental Therapeutics