Para-chlorophenylalanine, serotonin and killing behavior

Miczek, Klaus A.; Altman, Jack; Appel, James B.; Boggan, William O.

doi:10.1016/0091-3057(75)90043-x

Cited by 91 publications

(27 citation statements)

References 27 publications

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“…The compound was active at doses that are low, relative to those which have been used in other studies (e.g., Miczek et al 1975;Gartside et al 1992). This may have been due to a steep response curve for PPI after small changes in basal 5-HT levels (see above).…”

Section: Discussionmentioning

confidence: 79%

Depletion of 5-HT Disrupts Prepulse Inhibition in Rats Dependence on the Magnitude of Depletion, and Reversal by a 5-HT Precursor

Prinssen

Assié

Koek

et al. 2002

Neuropsychopharmacology

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The 5-HT 1A agonist 8-OH-DPAT has been reported to disrupt prepulse inhibition (PPI) of the acoustic startle reflex after local administration into the raphe nuclei. Because it is likely that 8-OH-DPAT disrupted PPI by activation of somatodendritic inhibitory receptors, and thereby, via a decrease in 5-HT neurotransmission, we tested whether chronic, drug-induced, depletions of 5-HT have similar effects. Rats were drug-treated for three consecutive days and tested in a short PPI paradigm on day 4, and retested 2 h later, after acute saline or drug administration. Repeated treatment with the 5-HT synthesis inhibitor p -chlorophenylalanine methyl ester (PCPA; 160 mg/kg) produced a small, but significant, attenuation of PPI, and a large decrease in extracellular 5-HT levels in the hippocampus, as measured in independent microdialysis experiments. An even larger depletion of 5-HT was obtained by substituting the 3 rd PCPA administration with the 5-HT releaser d-fenfluramine (10 mg/kg); this combined treatment nearly abolished PPI in the majority of animals. The involvement of 5-HT in the latter effects was confirmed by the finding that low doses of the 5-HT precursor 5-hydroxy- Microdialysis; Serotonin; Prepulse inhibition (PPI) of the startle response refers to the phenomenon that a startle response to a strong stimulus is reduced when this stimulus is preceded by a small prestimulus within a short time period (Graham 1975). The paradigm has gained interest both clinically and preclinically as it was observed that certain patient populations such as schizophrenics, and animals treated with psychotogenics, show attenuated PPI (Swerdlow et al. 1986;Geyer and Braff 1987). Early preclinical pharmacological studies of the mechanisms underlying PPI focused mainly on dopamine, but also on 5-HT, which appears to play an important role. For example, pharmacologically-induced release of 5-HT disrupts PPI in the rat (Padich et al. 1996;Martinez and Geyer 1997). More than one subtype of 5-HT receptor may be involved in these effects as selective stimulation of 5-HT 2A (Sipes and Geyer 1995;Padich et al. 1996), 5-HT 1B Geyer 1994, 1996), and 5-HT 1A receptors (Rigdon and Weatherspoon 1992;Sipes and Geyer 1995) disrupts PPI in the rat. In contrast to the extensive examination of increased function, the effects of de- (Sharp and Hjorth 1990;Blier et al. 1998). The finding that the 5-HT 1A agonist 8-OH-DPAT disrupts PPI after local administration in the raphe nuclei (Sipes and Geyer 1995), the main 5-HT neuron-containing nuclei, suggests that it acts on 5-HT 1A somatodendritic receptors, i.e., via a decrease in 5-HT neurotransmission. Here, we further studied whether decreases in 5-HT levels are indeed able to alter PPI, by examining the effects of chronic, drug-induced, 5-HT depletions. We first examined the effects of repeated administration of the 5-HT synthesis inhibitor p -chlorophenylalanine (PCPA), because this reportedly leads to a large and selective depletion of 5-HT (cf., Koe and Weissman 1966;Sarnek and Baran 1975;Ba...

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Section: Discussionmentioning

confidence: 79%

Depletion of 5-HT Disrupts Prepulse Inhibition in Rats Dependence on the Magnitude of Depletion, and Reversal by a 5-HT Precursor

Prinssen

Assié

Koek

et al. 2002

Neuropsychopharmacology

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“…), i.e. at a regimen previously shown to decrease serotonin content to 5-10 % of original levels (Miczek et al 1975). …”

Section: Drug Treatmentmentioning

confidence: 99%

“…in a dose regimen that has previously been shown to cause a marked reduction in serotonin levels throughout the brain while leaving catecholamine levels intact (Koe and Weissman 1966;Miczek et al 1975;Edén et al 1979).…”

Section: Introductionmentioning

confidence: 99%

Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat

et al. 2013

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“…However, this view has received little attention. According to this hypothesis, aggressive and sexual behavior in castrated male mice could be restored by administration of drugs that increase the level of arousal, e.g., parachlorophenylalanine (PCPA); PCPA is a potent serotonin (5-HT) antagonist which specifically depletes brain serotonin [Hartmann and Geller, 1971;Koe and Weissman, 1966;Miczek et al, 1975] and leads to increased aggression [Buchanan et al, 1994;Valzelli et al, 1981] and sexual behavior [Dahlöf and Larsson, 1979;Salis and Dewsbury, 1971;Singer, 1972;Södersten et al, 1976;Tsutsui et al, 1994;van de Poll et al, 1977;Yamanouchi and Kakeyama, 1992]. If this drug were found to restore aggressive and sexual reactions in a manner corresponding to testosterone (T) [Michael and Zumpe, 1993], this would suggest that the mediating mechanism here would be the level of arousal instead of some specific influence of T. It has been found that T stimulates male sexual activity, whereas 5-HT is assumed to inhibit it [Emery and Larsson, 1979;Foreman et al, 1989;Gorzalka et al, 1990;Södersten et al, 1950], and these opposite effects of T and 5-HT may be interrelated Wilson et al, 1991].…”

Section: Introductionmentioning

confidence: 99%

The relationship between aggressive and sexual behavior in male mice: Effects of testosterone and parachlorophenylalanine

Korpela

Sandnabba

1998

Aggr. Behav.

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Para-chlorophenylalanine, serotonin and killing behavior

Cited by 91 publications

References 27 publications

Depletion of 5-HT Disrupts Prepulse Inhibition in Rats Dependence on the Magnitude of Depletion, and Reversal by a 5-HT Precursor

Depletion of 5-HT Disrupts Prepulse Inhibition in Rats Dependence on the Magnitude of Depletion, and Reversal by a 5-HT Precursor

Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat

The relationship between aggressive and sexual behavior in male mice: Effects of testosterone and parachlorophenylalanine

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