Alpha-methylDOPA dissociates hypertension, cardiovascular reactivity and emotional behavior in spontaneously hypertensive rats

LeDoux, Joseph E.; Sakaguchi, Akira; Reis, Donald J.

doi:10.1016/0006-8993(83)91067-3

Cited by 16 publications

(3 citation statements)

References 16 publications

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“…LeDoux and co-workers, 24 who observed a similar response following i.p. injection of methyldopa in SHR, suggested that the tachycardiac response might be activated reflexly in response to baroreceptor stimulation accompanying the fall in arterial pressure.…”

Section: Discussionmentioning

confidence: 54%

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats.

Buccafusco¹

1984

Hypertension

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SUMMARY Chemical stimulation of brain cholinergic neurons in many species can produce hypertension. Recent studies in this laboratory have demonstrated that clonidine inhibits this central cholinergic pressor response by inhibiting the biosynthesis of brain acetylcholine. This study was designed to determine whether methyldopa, like clonidine, could inhibit brain cholinergic neurons involved in cardiovascular regulation in freely-moving spontaneously hypertensive rats (SHR). Intravenous (i.v.) injection of methyldopa (50-200 mg/kg) produced a dose-related fall in blood pressure (29/15-54/33 mm Hg) in SHR. Intracerebroventricular (i.c.v.) injection of hemicholinium-3 (HC-3) in SHR evoked a fall in arterial pressure through inhibition of acetylcholine synthesis. Doses of HC-3 (10 /ng, or 15 pLf>, i.c.v.) and methyldopa (50 mg/kg, i.v.) were administered to produce small reductions in arterial pressure in SHR (7-14 mm Hg diastolic, respectively). When the two agents were injected simultaneously, however, a greater than additive response was obtained (p < 0.05). Central injection of echothiophate (a long-acting cholinesterase inhibitor) to potentiate brain cholinergic activity resulted in a sustained hypertensive response (>40 mm Hg) in SHR for at least 150 minutes. Simultaneous injection of or pretreatment with methyldopa (100 mg/kg, i.v.) inhibited the pressor response to echothiophate over a time course similar to its antihypertensive response in untreated SHR. Methyldopa, however, was completely ineffective in altering the hypertensive response to central injection of carbachol (1 /xg, i.c.v.). This difference in methyldopa susceptibility between the indirect-acting (echothiophate) and direct-acting (carbachol) cholinergic agonists may be related to an inhibiting effect of methyldopa on brain acetylcholine release. These data support our previous studies with clonidine and suggest a cholinergic component in the antihypertensive action of these drugs. 1 -2 These receptors, however, do not appear to be located either presynaptically or postsynaptically upon central adrenergic neurons, since the antihypertensive effect of clonidine is not affected by drug treatments which cause depletion of brain catecholamines or which destroy adrenergic nerve endings.3 " 3 Likewise the hypotensive action of methyldopa is unaffected following severe depletion of brain catecholamines. 6 Recent studies in this laboratory haveFrom the

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Section: Discussionmentioning

confidence: 54%

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats.

Buccafusco¹

1984

Hypertension

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“…Unaware of their effects on DA, Brady (1956) first demonstrated the effects of reserpine and amphetamine on fear conditioning. The initial experiments were followed by numerous studies using classic DAergic drugs including psychostimulants, antipsychotics and DA analogues (Anisman, 1977;Harvey & Gormezano, 1981;Kumar, 1971a;1971b;LeDoux et al, 1983). Initial claims of DA's involvement in fear conditioning were refuted due to the non-selective binding affinity profiles of the drugs used.…”

Section: Dopamine and Fear Conditioningmentioning

confidence: 99%

50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

Hamati

Ahrens

Holahan

et al. 2023

Preprint

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Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gather the vast evidence for a role of dopamine in the simplest form of aversive learning: passive aversive conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine in order to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic, and optogenetic approaches now provide causal evidence for dopamine’s role in these learning processes. Dopamine neurons encode fear and extinction-related information and convey the signal via activation of D1, D2, D3, and D4 receptor sites particularly in the amygdala, prefrontal cortex, and striatum in order to continuously form, consolidate, retrieve, and update fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of passive aversive conditioning and contributes in a way that is comparable to its role in encoding reward.

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“…Unaware of their effects on DA, Brady (1956) first demonstrated the effects of reserpine and amphetamine on fear conditioning. The initial experiments were followed by numerous studies using classic DAergic drugs including psychostimulants, antipsychotics and DA analogues (Anisman, 1977;Harvey & Gormezano, 1981;Kumar, 1971aKumar, , 1971bLeDoux et al, 1983). Initial claims of DA's involvement in fear conditioning were refuted due to the non-selective binding affinity profiles of the drugs used.…”

Section: Da Fear Conditioning and Extinctionmentioning

confidence: 99%

65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review

Hamati,

Ahrens,

Shvetz

et al. 2023

Eur J of Neuroscience

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Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gathered the vast evidence of the role of dopamine in the simplest forms of aversive learning: classical fear conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic and optogenetic approaches now provide causal evidence for dopamine's role in these learning processes. Dopamine neurons encode conditioned stimuli during fear conditioning and extinction and convey the signal via activation of D1–4 receptor sites particularly in the amygdala, prefrontal cortex and striatum. The coordinated activation of dopamine receptors allows for the continuous formation, consolidation, retrieval and updating of fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of classical fear conditioning and extinction and contributes in a way that is comparable to its role in encoding reward.

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Alpha-methylDOPA dissociates hypertension, cardiovascular reactivity and emotional behavior in spontaneously hypertensive rats

Cited by 16 publications

References 16 publications

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats.

Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats.

50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review

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