Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro

Z. Z. Pan, John Williams

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Intracellular recordings of membrane potential were made from neurons in nucleus dorsal raphe in the rat brain slice. Cocaine (300 nM-30 μM) caused a concentration-dependent hyperpolarization of the membrane potential, with a maximum effect of 13.3 ± 2.2 mV (N = 6) and an EC50 of 4.2 μM. This action was antagonized by spiperone (1 μM), suggesting that the hyperpolarization was mediated indirectly througgh endogenous 5-hydroxytryptamine (5-HT). Cocaine (300 nM) increased the time constant for decay (τ2) of the 5-HT inhibitory postsynaptic potential (IPSP) from 432 ± 57 msec to 708 ± 81 msec (N = 14); 10 μM increased τ2 by about 9-fold. Amphetamine (100 nM-10 μM) caused a depolarization that was antagonized by prazosin (100 nM). In slices taken from reserpine-treated animals (5 mg/kg, 12 hr), the 5-HT-mediated IPSP, the noradrenaline-mediated slow excitatory postsynaptic potential and the amphetamine-induced depolarization were absent. These results indicate that the amphetamine-induced depolarization resulted from the release of endogenous noradrenaline. In the presence of prazosin (100 nM), amphetamine caused a hyperpolarization at a threshold concentration of 10 μM, had an EC50 of 26 μM and a maximum effect of 10 ± 0.9 mV (N = 8). This hyperpolarization as well as the cocaine-induced hyperpolarization were not reduced by prior treatment with reserpine. Amphetamine (10 μM) caused a 2.2-fold increase in the time constant of decay of the IPSP with no change in the amplitude. At a concentration of 30 μM the amplitude was reduced from 12.7 ± 0.9 mV (N = 10) to 2.0 ± 0.2 mV (N = 9) by amphetamine. Cocaine prolonged the IPSP and hyperpolarized the membrane potential. The prolongation of the IPSP resulted from inhibition of 5-HT uptake. The hyperpolarization resulted from the accumulation of spontaneously released 5-HT in the slice. Amphetamine had a similar hyperpolarizing action at about 10-fold higher concentrations and a weak effect on the duration of the IPSP. The results suggest that the major actions of cocaine and amphetamine on dorsal raphe neurons are different. Cocaine was inhibitory by enhancing 5-HT actions, whereas amphetamine caused an excitation through release of noradrenaline.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume251
Issue number1
StatePublished - 1989

Fingerprint

Amphetamine
Cocaine
Inhibitory Postsynaptic Potentials
Neurons
Serotonin
Membrane Potentials
Norepinephrine
Prazosin
Reserpine
Dorsal Raphe Nucleus
In Vitro Techniques
Spiperone
Intracellular Membranes
Excitatory Postsynaptic Potentials
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro. / Pan, Z. Z.; Williams, John.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 251, No. 1, 1989, p. 56-62.

Research output: Contribution to journalArticle

@article{d14fdf8d052f4251b5ecf2e7b82ba4e1,
title = "Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro",
abstract = "Intracellular recordings of membrane potential were made from neurons in nucleus dorsal raphe in the rat brain slice. Cocaine (300 nM-30 μM) caused a concentration-dependent hyperpolarization of the membrane potential, with a maximum effect of 13.3 ± 2.2 mV (N = 6) and an EC50 of 4.2 μM. This action was antagonized by spiperone (1 μM), suggesting that the hyperpolarization was mediated indirectly througgh endogenous 5-hydroxytryptamine (5-HT). Cocaine (300 nM) increased the time constant for decay (τ2) of the 5-HT inhibitory postsynaptic potential (IPSP) from 432 ± 57 msec to 708 ± 81 msec (N = 14); 10 μM increased τ2 by about 9-fold. Amphetamine (100 nM-10 μM) caused a depolarization that was antagonized by prazosin (100 nM). In slices taken from reserpine-treated animals (5 mg/kg, 12 hr), the 5-HT-mediated IPSP, the noradrenaline-mediated slow excitatory postsynaptic potential and the amphetamine-induced depolarization were absent. These results indicate that the amphetamine-induced depolarization resulted from the release of endogenous noradrenaline. In the presence of prazosin (100 nM), amphetamine caused a hyperpolarization at a threshold concentration of 10 μM, had an EC50 of 26 μM and a maximum effect of 10 ± 0.9 mV (N = 8). This hyperpolarization as well as the cocaine-induced hyperpolarization were not reduced by prior treatment with reserpine. Amphetamine (10 μM) caused a 2.2-fold increase in the time constant of decay of the IPSP with no change in the amplitude. At a concentration of 30 μM the amplitude was reduced from 12.7 ± 0.9 mV (N = 10) to 2.0 ± 0.2 mV (N = 9) by amphetamine. Cocaine prolonged the IPSP and hyperpolarized the membrane potential. The prolongation of the IPSP resulted from inhibition of 5-HT uptake. The hyperpolarization resulted from the accumulation of spontaneously released 5-HT in the slice. Amphetamine had a similar hyperpolarizing action at about 10-fold higher concentrations and a weak effect on the duration of the IPSP. The results suggest that the major actions of cocaine and amphetamine on dorsal raphe neurons are different. Cocaine was inhibitory by enhancing 5-HT actions, whereas amphetamine caused an excitation through release of noradrenaline.",
author = "Pan, {Z. Z.} and John Williams",
year = "1989",
language = "English (US)",
volume = "251",
pages = "56--62",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro

AU - Pan, Z. Z.

AU - Williams, John

PY - 1989

Y1 - 1989

N2 - Intracellular recordings of membrane potential were made from neurons in nucleus dorsal raphe in the rat brain slice. Cocaine (300 nM-30 μM) caused a concentration-dependent hyperpolarization of the membrane potential, with a maximum effect of 13.3 ± 2.2 mV (N = 6) and an EC50 of 4.2 μM. This action was antagonized by spiperone (1 μM), suggesting that the hyperpolarization was mediated indirectly througgh endogenous 5-hydroxytryptamine (5-HT). Cocaine (300 nM) increased the time constant for decay (τ2) of the 5-HT inhibitory postsynaptic potential (IPSP) from 432 ± 57 msec to 708 ± 81 msec (N = 14); 10 μM increased τ2 by about 9-fold. Amphetamine (100 nM-10 μM) caused a depolarization that was antagonized by prazosin (100 nM). In slices taken from reserpine-treated animals (5 mg/kg, 12 hr), the 5-HT-mediated IPSP, the noradrenaline-mediated slow excitatory postsynaptic potential and the amphetamine-induced depolarization were absent. These results indicate that the amphetamine-induced depolarization resulted from the release of endogenous noradrenaline. In the presence of prazosin (100 nM), amphetamine caused a hyperpolarization at a threshold concentration of 10 μM, had an EC50 of 26 μM and a maximum effect of 10 ± 0.9 mV (N = 8). This hyperpolarization as well as the cocaine-induced hyperpolarization were not reduced by prior treatment with reserpine. Amphetamine (10 μM) caused a 2.2-fold increase in the time constant of decay of the IPSP with no change in the amplitude. At a concentration of 30 μM the amplitude was reduced from 12.7 ± 0.9 mV (N = 10) to 2.0 ± 0.2 mV (N = 9) by amphetamine. Cocaine prolonged the IPSP and hyperpolarized the membrane potential. The prolongation of the IPSP resulted from inhibition of 5-HT uptake. The hyperpolarization resulted from the accumulation of spontaneously released 5-HT in the slice. Amphetamine had a similar hyperpolarizing action at about 10-fold higher concentrations and a weak effect on the duration of the IPSP. The results suggest that the major actions of cocaine and amphetamine on dorsal raphe neurons are different. Cocaine was inhibitory by enhancing 5-HT actions, whereas amphetamine caused an excitation through release of noradrenaline.

AB - Intracellular recordings of membrane potential were made from neurons in nucleus dorsal raphe in the rat brain slice. Cocaine (300 nM-30 μM) caused a concentration-dependent hyperpolarization of the membrane potential, with a maximum effect of 13.3 ± 2.2 mV (N = 6) and an EC50 of 4.2 μM. This action was antagonized by spiperone (1 μM), suggesting that the hyperpolarization was mediated indirectly througgh endogenous 5-hydroxytryptamine (5-HT). Cocaine (300 nM) increased the time constant for decay (τ2) of the 5-HT inhibitory postsynaptic potential (IPSP) from 432 ± 57 msec to 708 ± 81 msec (N = 14); 10 μM increased τ2 by about 9-fold. Amphetamine (100 nM-10 μM) caused a depolarization that was antagonized by prazosin (100 nM). In slices taken from reserpine-treated animals (5 mg/kg, 12 hr), the 5-HT-mediated IPSP, the noradrenaline-mediated slow excitatory postsynaptic potential and the amphetamine-induced depolarization were absent. These results indicate that the amphetamine-induced depolarization resulted from the release of endogenous noradrenaline. In the presence of prazosin (100 nM), amphetamine caused a hyperpolarization at a threshold concentration of 10 μM, had an EC50 of 26 μM and a maximum effect of 10 ± 0.9 mV (N = 8). This hyperpolarization as well as the cocaine-induced hyperpolarization were not reduced by prior treatment with reserpine. Amphetamine (10 μM) caused a 2.2-fold increase in the time constant of decay of the IPSP with no change in the amplitude. At a concentration of 30 μM the amplitude was reduced from 12.7 ± 0.9 mV (N = 10) to 2.0 ± 0.2 mV (N = 9) by amphetamine. Cocaine prolonged the IPSP and hyperpolarized the membrane potential. The prolongation of the IPSP resulted from inhibition of 5-HT uptake. The hyperpolarization resulted from the accumulation of spontaneously released 5-HT in the slice. Amphetamine had a similar hyperpolarizing action at about 10-fold higher concentrations and a weak effect on the duration of the IPSP. The results suggest that the major actions of cocaine and amphetamine on dorsal raphe neurons are different. Cocaine was inhibitory by enhancing 5-HT actions, whereas amphetamine caused an excitation through release of noradrenaline.

UR - http://www.scopus.com/inward/record.url?scp=0024460925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024460925&partnerID=8YFLogxK

M3 - Article

VL - 251

SP - 56

EP - 62

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -