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Biomedical subjects

J C Winter

Publications and source records attributed to J C Winter.

At least 55 records · Page 3Linked to original sources
PubMed1995

The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis.

Investigations conducted over the past 3 decades have demonstrated that serotonergic receptors, specifically the 5-HT2A and 5-HT2C subtypes, play an important role in the behavioral effects of hallucinogenic compounds. The present study was designed to determine the respective significance of these two receptors in the stimulus effects of LSD and (-)DOM in the rat. Specifically, the interactions of a series of serotonergic antagonists (risperidone, pirenpirone, metergoline, ketanserin, loxapine, LY53857, pizotyline, spiperone, cyprohepatadine, mesulergine, promethazine, and thioridazine) with the LSD stimulus and the (-)DOM stimulus in LSD-trained subjects was defined. From these data, IC50 values were determined for the inhibition of the LSD-appropriate responding elicited by either 0.1 mg/kg LSD (15-min pretreatment time) or 0.4 mg/kg (-)DOM (75-min pretreatment). In addition, the affinities of these antagonists for 5-HT2A and 5-HT2C receptors were determined in radioligand competition studies, 5-HT2A affinity correlated significantly with IC50 values for the blockade of the LSD (r = +0.75, P < 0.05) and (-)DOM (r = +0.95, P < 0.001) stimuli in the LSD trained subjects. 5-HT2C affinity did not correlate significantly with either series of IC50 values. These data indicate that (1) the stimulus effects of LSD, and (2) the substitution of (-)DOM for the LSD stimulus are mediated by agonist activity at 5-HT2A receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

Role of 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. II: Reassessment of LSD false positives.

In the context of animal studies of hallucinogens, an LSD-false positive is defined as a drug known to be devoid of hallucinogenic activity in humans but which nonetheless fully mimics LSD in animals. Quipazine, MK-212, lisuride, and yohimbine have all been reported to be LSD false positives. The present study was designed to determine whether these compounds also substitute for the stimulus effects of the more pharmacologically selective hallucinogen (-)DOM (0.56 mg/kg, 75-min pretreatment time). The LSD and (-)DOM stimuli fully generalized to quipazine (3.0 mg/kg) and lisuride (0.2 mg/kg), but only partially generalized to MK-212 (0.1-1.0 mg/kg) and yohimbine (2-20 mg/kg). In combination tests, pirenpirone (0.08 mg/kg), a compound with both D2 and 5-HT2A affinity, blocked the substitution of quipazine and lisuride for the (-)DOM stimulus. Ketanserin (2.5 mg/kg), an antagonist with greater than 1 order of magnitude higher affinity for 5-HT2A receptors than either 5-HT2C or D2 receptors, also fully blocked the substitution of these compounds for the (-)DOM stimulus, while the selective D2 antagonist thiothixene (0.1-1.0 mg/kg) failed to block the substitution of lisuride for the (-)DOM stimulus. These results suggest that quipazine and lisuride substitute for the stimulus properties of the phenylalkglamine hallucinogen (-)DOM via agonist activity at 5-HT2A receptors. In addition, these results suggest that 5-HT2A agonist activity may be required, but is not in itself sufficient, for indolamine and phenylalkglamine compounds to elicit hallucinations in humans. Finally, it is concluded that MK-212 and yohimbine are neither LSD nor (-)DOM false positives.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. III: The mechanistic basis for supersensitivity to the LSD stimulus following serotonin depletion.

The present study was designed to determine the effects of p-chlorophenylalanine (PCPA) and p-chloroamphetamine (PCA) administration on (1) the levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain, (2) the sensitivity of LSD-trained rats to the stimulus effects of LSD, and (3) the maximal levels of 5-HT2A and 5-HT2C receptor mediated phosphoinositide (PI) hydrolysis in rat brain. PCA and PCPA both produced a significant depletion of whole brain 5-HT and 5-HIAA concentrations. The depletion of serotonin with PCPA, but not PCA, resulted in supersensitivity of LSD-trained subjects to the stimulus effects of LSD. Neither PCPA nor PCA treatment altered the maximal level of 5-HT2A receptor-mediated PI hydrolysis. However, PCPA, but not PCA, treatment resulted in a significant upregulation (46%, P < 0.05) of the maximal level of 5-HT2C receptor mediated PI hydrolysis. These data suggest that upregulation of the 5-HT2C receptor mediates the supersensitivity to LSD discriminative stimulus which follows the depletion of central nervous system serotonin by PCPA.

Animals↗
PubMed1995

The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of m-chlorophenylpiperazine.

m-Chlorophenylpiperazine (mCPP), a major metabolite of the atypical antidepressant trazadone, has been observed to produce marked physiological and behavioral effects in both humans and animals. These effects have been attributed to the interaction of mCPP with serotonergic receptors. The present study was designed to characterize those interactions of mCPP with central serotonergic receptors which mediate mCPP-induced stimulus control. A series of serotonergic antagonists (mesulergine, pizotyline, ketanserin, spiperone, risperidone, ritanserin, metergoline, pirenpirone, and LY53857) was tested for the ability to block the mCPP stimulus. The affinity of these antagonists for 5-HT2A and 5-HT2C receptors was then correlated with maximal percent inhibition of the mCPP stimulus. Kd at the 5-HT2C receptor was inversely proportional (r = -0.75, P < 0.05), and Kd at the 5-HT2A receptor directly proportional (r = +0.67, P < 0.05) to the maximal percent inhibition of the mCPP stimulus. The 5-HT2C selectivity ratio [Kd(5-HT2A)/Kd(5-HT2C)] of the antagonists was directly proportional (r = +0.86, P < 0.01) to maximal percent inhibition of the mCPP stimulus. A multiple regressions analysis indicated that 81% of the variance in the ability of a given antagonist to block the mCPP stimulus could be predicted on the basis of its affinity for 5-HT2A and 5-HT2C receptors. It is concluded that the stimulus effects of mCPP are mediated predominantly by a combination of agonist activity at 5-HT2C receptors and antagonist activity at 5-HT2A receptors.

Animals↗
PubMed1995

The time-dependent stimulus effects of R(-)-2,5-dimethoxy-4-methamphetamine (DOM): implications for drug-induced stimulus control as a method for the study of hallucinogenic agents.

The pharmacodynamic characteristics of the stimulus effects of the hallucinogens d-LSD and (-)DOM were investigated in the rat. The stimulus control induced by (-)DOM (0.56 mg/kg) was significantly less stable at the 15-min pretreatment time than at the 75-min pretreatment time. In addition, (-)DOM (0.8 mg/kg) produced a time-dependent substitution for the LSD stimulus in LSD trained subjects (0.1 mg/kg, 15-min pretreatment time). As pretreatment times were increased, the substitution of (-)DOM (0.8 mg/kg) for the LSD stimulus increased, culminating in a maximal level of 99.5% LSD-appropriate responding at the 75-min pre-treatment time. A dose-response relationship for the substitution of (-)DOM (75-min pretreatment time) for the LSD stimulus, indicated that 0.2 mg/kg (-)DOM was the minimum dose which elicited greater than 90% LSD-appropriate responding. LSD (0.32 mg/kg, 15-min pretreatment time) fully substituted for (-)DOM in the (-)DOM trained subjects (0.56 mg/kg, 75-min pretreatment time). These findings suggest that the pharmacodynamic parameters of d-LSD and (-)DOM-induced stimulus control differ. The time of onset for the stimulus effects of (-)DOM is markedly longer than that of LSD in the rat.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

5-HT2C receptor-mediated phosphoinositide turnover and the stimulus effects of m-chlorophenylpiperazine.

The present study was designed to investigate the hypothesis that agonist interactions at 5-HT2C receptors mediate the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). Three structural classes of compounds have been described to stimulate increases in phosphoinositide (PI) hydrolysis at the 5-HT2C receptor site: phenylpiperazines, phenylalkylamines, and indolamines. Four representative phenylpiperazines, mCPP, TFMPP, MK-212 and quipazine, one phenylalkylamine, (-)DOM, and one indolamine, LSD, were employed in the present study. The efficacies of these compounds were defined (1) in vitro, with respect to their abilities to stimulate increases in PI hydrolysis in the choroid plexus, and (2) in vivo with respect to their abilities to substitute for the mCPP discriminative stimulus. In vitro intrinsic activity at the 5-HT2C site was expressed as a fraction of the maximal PI hydrolysis response elicited by serotonin (5-HT). MK-212 (fractional efficacy = 1.1) and (-)DOM (0.77) were full agonists, while mCPP (0.72), LSD (0.27), quipazine (0.24), and TFMPP (0.22) were partial agonists with respect to the stimulation of PI hydrolysis at the 5-HT2C receptor. In vivo, each of the phenylpiperazines fully substituted for the mCPP stimulus, while (-)DOM (75%), and LSD (67%) elicited only partial substitution. While compounds with agonist activity at the 5-HT2C receptor in vitro substitute for the mCPP stimulus in vivo, no clear relationship exists between in vitro intrinsic activity at the 5-HT2C receptor with respect to the stimulation of PI turnover and maximal substitution for the mCPP stimulus in vivo. The present data suggest that mCPP elicits a compound stimulus which is mediated by agonist interactions at the 5-HT2C receptor and possibly additional interactions with 5-HT2A, 5-HT3, and/or 5-HT1B receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

The interactions of typical and atypical antipsychotics with the (-)2, 5,-dimethoxy-4-methamphetamine (DOM) discriminative stimulus.

The present study was designed to test the hypothesis that atypical, but not typical, antipsychotics produce a functional in vivo blockade of 5-HT2A receptors. The magnitude of functional in vivo 5-HT2A receptor blockade elicited by representative compounds from each of the six major structural classes of typical antipsychotics, and the representative atypical antipsychotics clozapine and risperidone, was indicated by their respective abilities to block the stimulus effects of the phenylalkylamine hallucinogen (-)DOM in the rat. Chlorpromazine, thioridazine, fluphenazine, thiothixene and haloperidol did not produce a significant antagonism of the (-)DOM stimulus. The benzoxapine, loxapine (60%), and the atypical dibenzodiazepine, clozapine (62%), partially blocked and risperidone fully blocked (100%) the (-)DOM stimulus. None of these agents elicited significant levels of (-)DOM-appropriate responding when administered alone. These results indicate that the typical antipsychotics, with the exception of lozapine, fail to produce effective in vivo antagonism of 5-HT2A receptors at doses compatible with the preservation of operant behavior. In contrast, the atypical antipsychotics clozapine and risperidone elicit effective in vivo antagonism of 5-HT2A receptors without severe behavioral disruption. Thus, these data are supportive of the hypothesis that the mechanism of action of atypical, but not typical, antipsychotics involves the antagonism of 5-HT2A receptors in vivo.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1994

Serotonergic control of androgen-induced dominance.

The present study investigates the role of serotonergic systems in anabolic steroid-induced aggression. An animal model of aggressive dominance was used to assess the chronic effects of testosterone propionate. When rats that had become dominant following administration of testosterone propionate received serotonergic agonists with selectivity for the 5-HT1A receptor (8-OH-DPAT, buspirone, gepirone), the 5-H1B receptor (eltoprazine, TFMPP), or the 5-HT2A/2C receptor (DOM), a dose-dependent decrease in dominance was demonstrated. Pretreatment with three serotonergic antagonists (pizotyline, pirenpirone, and pindolol) blocked agonist-induced reductions in dominance in varying degrees. Nonserotonergic agonists with CNS depressant effects were also tested in dominant animals. The benzodiazepine, chlordiazepoxide, did not reduce dominance except at doses that interfered with motor behavior. The opioid agonist, morphine, dose dependently decreased dominance, but this effect was reversible with administration of the serotonergic antagonist, pirenpirone, suggesting the antidominant effect of morphine had a serotonergic component. Biochemical experiments demonstrated that following chronic testosterone propionate, there was a decrease in levels of 5-HT and 5-HIAA in the hippocampus but not in the striatum or the frontal cortex. Chronic testosterone propionate also caused an increase in the affinity of [3H]8-OH-DPAT for the 5-HT1A receptor but no corresponding change in the density of 5-HT1A binding sites in the hippocampus. There was also no change in the properties of the 5-HT2 receptor in the frontal cortex following chronic testosterone propionate. These data suggest that serotonergic systems may play an important role in the control of anabolic steroid-induced aggressive dominance.

Aggression↗
PubMed1994

Interactions of clozapine with the stimulus effects of DOM and LSD.

Two groups of rats were trained with the 5-HT2 agonists 2,5-dimethoxy-4-methylamphetamine (DOM) or lysergic acid diethylamide (LSD) in a two-lever discrimination task. Tests of generalization and antagonism were then carried out with clozapine. DOM did not generalize to clozapine. Partial antagonism of DOM was observed with 0.3, 1, and 2 mg/kg clozapine and statistically significant full antagonism with 3 mg/kg. LSD did not fully generalize to clozapine. Partial antagonism of LSD was observed with 3 and 4 mg/kg clozapine. Because clozapine is known to block muscarinic as well as 5-HT2 receptors, atropine was studied in DOM-trained rats. DOM partially generalized to 3 mg/kg atropine. Partial attenuation of DOM stimulus effects was observed with 3 mg/kg atropine, and no attenuation with 5 mg/kg. A combination of 2 mg/kg clozapine and 3 mg/kg atropine vs. DOM produced response suppression in five of seven rats. The atropine test results do not exclude the possibility of an antimuscarinic component in the observed attenuation of DOM and LSD stimulus effects by clozapine.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1993

Studies of the biochemical basis for the discriminative properties of 8-hydroxy-2-(di-n-propylamino)tetralin.

The ability of a series of compounds to mimic the stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was compared to: (1) the affinity of these compounds for the 5-HT1A receptor; and (2) their efficacy to inhibit forskolin-stimulated adenylate cyclase activity. Although for nine compounds (flesinoxan, MDL 73005EF, gepirone, ipsapirone, buspirone, tandospirone, yohimbine, L 657,743 and rauwolscine) complete cross generalization was associated with high affinity for the 5-HT1A receptor, eltoprazine, d-lysergic acid diethylamide and BMY 7378 had pKD > 7.44, but did not show complete mimicry of 8-OH-DPAT. In addition, indorenate had a pKD of 7.88, yet the behavioral response was indistinguishable from the saline control. Because the above data indicated that affinity for the 5-HT1A receptor was necessary, but not sufficient for a receptor ligand to mimic 8-OH-DPAT, the in vitro efficacy of the various compounds at the 5-HT1A receptor was determined by measuring inhibition of forskolin-stimulated adenylate cyclase activity in hippocampal membranes. For a series of drugs (gepirone, ipsapirone, flesinoxan, buspirone, tandospirone, yohimbine, L 657,743 and rauwolscine) significant inhibition of forskolin-stimulated adenylate cyclase activity was observed, and these same drugs showed complete cross generalization. However, BMY 14802 and MDL 73005EF did not alter adenylate cyclase activity, yet completely mimicked the stimulus properties of 8-OH-DPAT. Eltoprazine had significant efficacy in inhibiting forskolin-stimulated adenylate cyclase activity, but only 30% of the responses following administration of this drug were on the 8-OH-DPAT-appropriate lever. Furthermore, although indorenate inhibited hippocampal adenylate cyclase activity, the behavioral response to this compound was indistinguishable from the saline control.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Antagonism of the stimulus effects of yohimbine and 8-hydroxydipropylaminotetralin.

Stimulus control was established in rats using either 8-hydroxy-2-[di-n-propylamino]tetralin (DPAT) (0.2 mg/kg) or yohimbine (3 mg/kg). Tests were then conducted with purported antagonists at 5-hydroxytryptamine1A (5-HT1A) receptors. Drugs studied were NAN-190, [+/-]-pindolol, and [-]-alprenolol. In addition, each drug was characterized in terms of its affinity for 5-HT1A and alpha 2-adrenoceptors by means of radioligand binding techniques. None of the antagonists tested provided complete blockade of the stimulus effects of either DPAT or yohimbine. However, [+/-]-pindolol produced a statistically significant intermediate degree of antagonism of both DPAT and yohimbine. The affinities of DPAT, yohimbine, and NAN-190 for the 5-HT1A and alpha 2-adrenergic receptors, respectively, were sufficiently high to lead to some ambiguity of interpretation of the behavioral data. However, the results with [+/-]-pindolol, which has high affinity for the 5-HT1A receptor (34 nM) and negligible affinity for the alpha 2-adrenoceptor (24,600 nM), indicate that a significant component of yohimbine-induced stimulus control is mediated by the 5-HT1A receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Discriminative stimulus properties of m-chlorophenylpiperazine.

Stimulus control was established in a group of 10 rats using a dose of m-chlorophenylpiperazine (MCPP) of 0.8 mg/kg, administered IP, 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 27 sessions was required to reach criterion performance. Response rates were significantly suppressed by the training dose of MCPP (14 responses/min) as compared with saline sessions (38 responses/min). Subsequent to the establishment of stimulus control, tests of generalization were conducted with m-trifluoromethylphenylpiperazine (TFMPP), 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969). MCPP generalized completely to MK-212 and TFMPP at doses of the latter drugs of 0.7 and 1.0 mg/kg, respectively. Maximum generalization to RU-24969 was 67% at a dose of 1.0 mg/kg but only 4 of 10 subjects completed the test session. The present results indicate that MCPP is efficacious as a discriminative stimulus. In addition, because of MCPP's relative selectivity for the 5-hydroxytryptamine c(5-HT1C) receptor subjects trained with MCPP may prove valuable in assessing the respective functional contributions of 5-HT1C sites to the actions of a variety of serotonergic agents.

Animals↗
PubMed1992

Reversal of testosterone-induced dominance by the serotonergic agonist quipazine.

Anabolic steroids and other androgens, such as testosterone propionate (TP), have a facilitatory role in the expression of aggressive behavior. Based upon literature indicating an inverse relationship between aggression and the central neurotransmitter serotonin (5-HT), the present study was undertaken to investigate the role of 5-HT in androgen-induced aggression. In this study, an animal model of aggression involving competition between male rat pairs for sugar pellets was used to investigate the effects of TP. When TP was administered daily (30 mg/kg) to nondominant rats, these animals became dominant. Dominant behavior was found to be stable throughout the study with continued daily administration of TP. To test the serotonergic component of TP-induced aggression, the serotonergic agonist 2-(1-piperazinyl) quinolone dimaleate (quipazine) was administered acutely to TP-dominant rats. Quipazine dose dependently reduced aggressive dominance in TP-dominant rats, as well as in naturally dominant rats. When the serotonergic antagonists pirenpirone or pizotyline were coadministered with quipazine to either group of dominant rats, they blocked the effect of quipazine in reducing dominance. However, when 1-[1H-Indol-4-yloxy]-3-[isopropylamino]-2-propanol (pindolol), a drug that acts at both beta-adrenergic receptors and at 5-HT1A and 5-HT1B receptors, was coadministered with quipazine there was a reversal of the quipazine effect on aggression only in TP-dominant rats. These results indicate that androgen-induced aggression may involve a complex alteration in serotonergic neurotransmission.

Anabolic Agents↗
PubMed1992

Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD.

The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with either yohimbine (6 mg/kg), DOM (0.6 mg/kg), or LSD (0.1 mg/kg) vs. no treatment in a two-lever discrimination task. Tests of generalization were then conducted with ibogaine. In yohimbine-trained animals, 39.7% of responses following ibogaine (15 mg/kg) were on the drug-appropriate lever, but this response level was not significantly different from no treatment-appropriate responding. A response distribution that was significantly different from responding under both drug and no treatment training conditions was observed in DOM-trained rats after administration of 15 mg/kg ibogaine. Pizotyline (BC-105) blocked all DOM-appropriate responding produced by ibogaine. In LSD-trained animals, 20 mg/kg ibogaine mimicked LSD. Pizotyline blocked LSD-appropriate responding produced by ibogaine in five of six animals. The present data suggest the involvement of 5-HT2 receptor activity, and the possibility of a 5-HT1A contribution, in the stimulus properties of ibogaine.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1992

Yohimbine as a serotonergic agent: evidence from receptor binding and drug discrimination.

Stimulus control was established in rats trained to discriminate either 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT) (0.2 mg/kg) or yohimbine (3 mg/kg) from saline. Tests of generalization were then conducted with a group of drugs thought to act via the 5-hydroxytryptamine1A (5-HT1A) receptor and a group of drugs thought to act as antagonists at alpha 2 adrenoceptors. In addition, each drug was characterized in terms of its affinity for 5-HT1A and alpha 2 adrenoceptors by means of radioligand binding techniques. It was observed that the stimulus effects of DPAT generalized fully to those of the alpha 2-adrenoceptor antagonists, yohimbine, rauwolscine and L-657,743, but not to idazoxan or atipamezole. The dissociation constants (Kd, nM) of the alpha 2-adrenoceptor antagonists at the 5-HT1A receptor were 74, 52, 80, 199 and 13,000, respectively. Thus, the discrimination data are explicable in terms of a direct action of yohimbine and some other alpha 2 adrenoceptor antagonists upon 5-HT1A receptors. In yohimbine-trained rats, full generalization to DPAT, flesinoxan and tandospirone was observed. In light of the negligible affinity of flesinoxan and tandospirone for the alpha 2 adrenoceptor (9000 and 8800 nM, respectively), and high affinity for the 5-HT1A receptor (0.3 and 43 nM, respectively), a mechanism mediated by the latter site is suggested. We would emphasize two implications of the present study. First, the present data suggest that rats trained with yohimbine as a discriminative stimulus generalize to drugs with minimal affinity for the alpha 2 adrenoceptor but with high affinity for 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Phencyclidine/SKF-10,047 binding sites: evaluation of function.

Results of correlation analyses comparing rank-order affinities with rank-order potencies of (+)SKF-10,047, phencyclidine (PCP), and several PCP analogs support the involvement of [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine binding sites (TCP sites) in mediating both the discriminative stimulus properties of PCP and production of 180 degrees perseveration in a 4-arm radial maze. For the same group of drugs, no significant relationship was found to exist between affinities at haloperidol-sensitive (+)[3H]SKF-10,047 binding sites (H-S-SKF sites) and potencies. Also, H-S-SKF sites were found to lack pharmacological selectivity and to be localized in the microsomal fraction of cells. It is concluded that TCP sites may represent receptors which mediate effects not only of PCP, but also of (+)SKF-10,047. In addition, the possibility that H-S-SKF sites may represent a type of membrane-bound enzyme is discussed.

Animals↗
PubMed1988

A comparison of the discriminative stimulus properties of l-5-hydroxytryptophan in the presence of either citalopram or Ro 4-4602.

The establishment of stimulus control by 5-HTP, the amino acid precursor for serotonin (5-HT), has been reported previously [1-3]. In the present investigation, two groups of rats were trained with 5-HTP versus saline in a 2-lever discrimination procedure. Prior to the administration of 5-HTP, subjects were pretreated with either Ro 4-4602, an inhibitor of peripheral decarboxylase (R-HTP), or citalopram, a specific 5-HT reuptake inhibitor (C-HTP). Neither C-HTP nor R-HTP was antagonized completely by either pirenperone or pizotyline. When C-HTP and R-HTP were tested in a third group of rats trained with LSD, complete generalization was not observed. The results of cross tests in the R-HTP and C-HTP groups with LSD, TFMPP, 8-OH-DPAT, C-HTP, and R-HTP indicate that the stimuli induced by R-HTP and C-HTP are similar but not identical. Taken together, these data suggest that 5-HTP produces a compound stimulus that is not readily explained in terms of either 5-HT1 or 5-HT2 receptors alone.

5-Hydroxytryptophan↗