Serotonergic mediation of fenfluramine discriminative stimuli in fawn-hooded rats.
*Discrimination Learning; 4-methylenedioxyamphetamine/pharmacology; Animals; Dose-Response Relationship; Drug; Fenfluramine/administration & dosage/*pharmacology; Fluoxetine/pharmacology; Ibogaine/pharmacology; Male; Methoxydimethyltryptamines/pharmacology; N-Methyl-3; Piperazines/pharmacology; Quipazine/pharmacology; Rats; Serotonin Agents/administration & dosage/*pharmacology; Serotonin Receptor Agonists/pharmacology; Serotonin/*metabolism; Sprague-Dawley
Fenfluramine, a drug that induces increased synaptic serotonin, was used to train Fawn-Hooded rats in a drug discrimination paradigm. This strain of rats is thought to possess a genetic serotonin storage abnormality. The intent of the study was to see if the Fawn-Hooded rat was similar or dissimilar to the more frequently used strain of Sprague-Dawley rat in its ability to learn to discriminate 2.0 mg/kg fenfluramine administered intraperitoneally. In addition, drugs presumed to work upon central serotonergic neurons were given to the fenfluramine-trained Fawn-Hooded rats to investigate if the cueing properties of the training drug generalized to other agents. Results indicate that the Fawn-Hooded rats learn to discriminate fenfluramine from its vehicle at the same rate, and with a similar sensitivity to lower doses, as do the Sprague-Dawley rats. Furthermore, fenfluramine was shown to completely generalize to MDMA (over 90%); TFMPP, m-CPP, quipazine and fluoxetine produced intermediate results (over 70%) and 5-MeODMT and ibogaine were vehicle-like (less than 70%). As these results coincide with those previously found in Sprague-Dawley rats, the conclusion is that the functional capacity to discriminate fenfluramine appears to be like that of other rat lines, and serotonergically-mediated, in the Fawn-Hooded rat. Suggestions to explain these results are offered and discussed.
Schechter M D
Life sciences
1997
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0024-3205(96)00668-6" target="_blank" rel="noreferrer noopener">10.1016/s0024-3205(96)00668-6</a>
Serotonergic involvement in the regulation of prolactin and vasoactive intestinal peptide mRNA expression in the rat anterior pituitary.
5-Hydroxytryptophan/pharmacology; alpha-Methyltyrosine; Animals; Anterior/*chemistry/drug effects/metabolism; Blotting; Bromocriptine/pharmacology; Gene Expression Regulation/drug effects/physiology; Genetic; Haloperidol/pharmacology; Ketanserin/pharmacology; Male; Messenger/*analysis/genetics; Methiothepin/pharmacology; Methoxydimethyltryptamines/pharmacology; Methyltyrosines/pharmacology; Northern; Pituitary Gland; Prolactin/analysis/*genetics/metabolism; Quipazine/pharmacology; Rats; RNA; Serotonin/*physiology; Sprague-Dawley; Time Factors; Transcription; Vasoactive Intestinal Peptide/analysis/*genetics/metabolism
These studies examined the contribution of serotonin (5-HT) to the control of prolactin (PRL) and vasoactive intestinal peptide (VIP) messenger RNA expression in rat anterior pituitary. Daily injection of rats with the biosynthetic precursor to serotonin, 5-hydroxytryptophan (5-HTP; 25 mg/kg, q.i.d.), resulted on day 5 in a 50% increase in the expression of PRL mRNA in the pituitary while at the same time reducing the levels of both the 1.0 and 1.7 kb VIP mRNA transcripts. Co-treatment of rats with 5-HTP plus the catecholamine biosynthesis inhibitor, alpha-methyl-tyrosine (alpha-MT; 150 mg/kg, q.d. x 2 days), or the dopamine receptor antagonist haloperidol (1.25 mg/kg, b.i.d. x 5 days), resulted in increases in pituitary PRL message levels that were greater than those observed with either anti-dopaminergic agent alone. In contrast, 5-HTP was unable to reverse the inhibition of PRL mRNA expression caused by treatment with the dopamine receptor agonist bromocriptine (2.5 mg/kg, b.i.d. x 5 days). Neither alpha-MT, haloperidol nor bromocriptine had a significant effect on pituitary VIP mRNA expression. Administration of the direct-acting 5-HT receptor agonist quipazine (5 mg/kg, b.i.d.) for 14 consecutive days caused a significant increase in pituitary PRL mRNA levels on day 1 and reached a plateau of 90% above control levels on days 7 and 14. VIP mRNA levels rose significantly on day 1 of quipazine treatment but thereafter fell to a minimum of 22% (1.0 kb) and 52% (1.7 kb) of control by day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Signs S A; Liu B; Wolford J; Carrillo A J
Molecular and cellular endocrinology
1994
1994-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0303-7207(94)90168-6" target="_blank" rel="noreferrer noopener">10.1016/0303-7207(94)90168-6</a>