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This study investigated whether exposure to cocaine during the preweaning period affects the behavioral response to administration of a challenge dose of quipazine, a relatively nonselective serotonin (5-HT) mixed agonist/antagonist, in adulthood. To determine whether selective inhibition of the 5-HT transporter during the preweaning period would produce a cocaine-like pattern of effects, another group of rats was given fluoxetine, a highly selective and potent inhibitor of the 5-HT transporter, and was tested along with the cocaine-treated rats. Male and female rats received 25 mg/kg cocaine HCl (82.5 mumol/kg), 25 mg/kg fluoxetine HCl (72.3 mumol/kg), or vehicle subcutaneous (s.c.) during postnatal days 11-20. Both treatments reduced weight gain during the injection period only. At 60 days of age, subjects were administered a single dose of quipazine (0, 0.4, or 1.0 mg/kg, s.c.) and placed in the Accuscan activity monitor for 1 h of behavioral recording. Overall, distance traveled, vertical activity, and time in the center of the chamber decreased during the initial time blocks of the session and vertical activity decreased with increasing doses of quipazine. Females in general showed greater overall activity levels than males as well as greater responsivity to quipazine. Preweaning cocaine exposure produced different effects in males and females. In males, cocaine enhanced the response to quipazine for vertical activity whereas it had no effect on quipazine-induced alterations on the other two behaviors. On the other hand, cocaine-treated females showed dampened dose-related quipazine responses across all behavioral measures. Fluoxetine administration produced a dampening of the quipazine effect for vertical activity and distance traveled in males and females. Therefore, these data indicate that cocaine administration during the preweaning period of development produced an increase in the effect of a serotonergic drug to alter vertical activity in males and a global dampening of the behavioral responses to that same drug in females. Preweaning fluoxetine treatment produced effects that resembled those produced by cocaine in females, a dampening of serotonergic responsivity, along with an overall decrease in locomotor activity. Because the majority of effects are seen during the initial portion of the behavioral session, a time of heightened activity in response to a novel environment, the data suggest that inhibition of the 5-HT transporter during the preweaning period alters serotonergic influences over novelty-induced activity but that brief periods of inhibition or other actions of cocaine, such as those at the catecholamine transporters, prevent this from happening, particularly in males.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9536459&dopt=Abstract
note: kwd match prozac online literature
Eur J Pharmacol. 1997 Dec 11;340(2-3):145-51.
Effect of quinine on autoreceptor-regulated serotonin release in the rat hippocampus.
Li MY, Reith ME.
Department of Biomedical and Therapeutic Sciences, College of Medicine, University of Illinois, Peoria 61656, USA.
The involvement of K+ channels in the autoregulation of terminal serotonin (5-hydroxytryptamine, 5-HT) release was investigated by microdialysis in the hippocampus of conscious rats. Extracellular 5-HT was increased concentration-dependently by the K+ channel blocker quinine (10, 100 and 1000 microM in perfusate), and tetrodotoxin (10 microM) but not fluoxetine (5 microM) exerted a partially attenuating influence. The 5-HT1/2/6 receptor antagonist methiothepin (50 microM) increased dialysate 5-HT, most likely through 5-HT1B autoreceptors tonically activated in the hippocampus of awake rats as opposed to the previously reported lack of effect 5-HT1B autoreceptor blockade in anesthetized rats. The effect of methiothepin was greatly reduced by preperfusion with quinine (100 microM), consonant with a role for quinine-sensitive K+ channels in the autoregulation of 5-HT release in the hippocampus by 5-HT receptor antagonism. In contrast, the reduction in dialysate 5-HT induced by the 5-HT1 receptor agonist RU 24969 (1 microM), in the presence of fluoxetine (5 microM), persisted in the co-presence of quinine, consonant with the involvement of (extrasynaptic?) 5-HT autoreceptors not coupled with quinine-sensitive K+ channels.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9537808&dopt=Abstract
note: kwd match prozac online literature
Eur J Pharmacol. 1999 Mar 5;368(2-3):277-83.
Pharmacological profile of neuroleptics at human monoamine transporters.
Tatsumi M, Jansen K, Blakely RD, Richelson E.
Mayo Clinic Jacksonville, FL 32224, USA.
Using radioligand binding techniques, we determined the equilibrium dissociation constants (K(D)) for 37 neuroleptics and one metabolite of a neuroleptic (haloperidol metabolite) for the human serotonin, norepinephrine, and dopamine transporters with [3H]imipramine, [3H]nisoxetine, and [3H]WIN35428, respectively. Among neuroleptics, the four most potent compounds at the human serotonin transporter were triflupromazine, fluperlapine, chlorpromazine, and ziprasidone (K(D) 24-39 nM); and at the norepinephrine transporter, chlorpromazine, zotepine, chlorprothixene, and promazine (K(D) 19-25 nM). At the human dopamine transporter, only pimozide (K(D) = 69+/-3) ziprasidone (K(D) = 76+/-5) had notable potency. These data may be useful in predicting therapeutic and adverse effects, including drug interactions of neuroleptics.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10193665&dopt=Abstract
note: kwd match prozac online literature
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