Distribution of substance P-like immunoreactivity in the central nervous system of the rat—I. Cell bodies and nerve terminals

Two dopamine receptors: Biochemistry, physiology and pharmacology

Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors

Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine-containing neurons in the rat central nervous system.

Considerable evidence from preclinical and clinical investigations implicates disturbances of brain dopamine (DA) function in the pathophysiology of several psychiatric and neurologic disorders. We describe a neural model that may help organize theseindependent experimental observations. Cortical regions classically associated with the limbic system interact with infracortical structures, including the nucleus accumbens, ventral pallidum, and dorsomedial nucleus of the thalamus. In our model, overactivity in forebrain DA systems results in the loss of lateral inhibitory interactions in the nucleus accumbens, causing disinhibition of pallidothalamic efferents; this in turn causes rapid changes and a loss of focused corticothalamic activity in cortical regions controlling cognitive and emotional processes. These effects might be manifested clinically by some symptoms of psychoses. Underactivity of forebrain DA results in excess lateral inhibition in the nucleus accumbens, causing tonic inhibition of pallidothalamic efferents; this perpetuates tonic corticothalamic activity and prevents the initiation of new activity in other critical cortical regions. These effects might be manifested clinically by some symptoms of depression. This model parallels existing explanations for the etiology of several movement disorders, and may lead to testable inferences regarding the neural substrates of specific psychopathologies.

Dopamine, schizophrenia, mania, and depression: Toward a unified hypothesis of cortico-striatopallido-thalamic function

Extracellular recordings were made from neurones in the mesencephalic reticular formation and substantia nigra of the rat which was anaesthetized with urethane 1.5–2 g/kg i.p. Out of 44 cells tested 42 were excited by Substance P applied iontophoretically and in some cases this excitation was rapid. Evidence is presented for Substance P as a putative excitatory transmitter onto reticular and nigral neurones possibly released from primary sensory afferents.

The action of substance P on mesencephalic reticular and substantia nigral neurones of the rat.

1 The effects of gamma-aminobutyric acid (GABA) and related drugs on the isolated anococcygeus muscle of the rat were determined. 2 GABA caused a dose-related inhibition of the electrically-evoked twitch response. 3 The maximum response to GABA was a 56.8% depression of twitch response, with an EC50 of 0.68 microM. 4 (+/-)-Baclofen mimicked the effect of GABA (EC50 0.9 microM). (+)-Baclofen was more than 100 times less active than (--)-baclofen. 5 The response to GABA was unaffected by picrotoxin or bicuculline but was antagonized by 5-aminovaleric acid (0.5) mM). 6 Our results suggest that GABAB receptors are present on motor nerve terminals in the rat anococcygeus muscle and that 5-aminovaleric acid is an antagonist of these receptors.

PRESYNAPTIC γ‐AMINOBUTYRIC ACID RECEPTORS IN THE RAT ANOCOCCYGEUS MUSCLE AND THEIR ANTAGONISM BY 5‐AMINOVALERIC ACID

Neurones in the substantia nigra of the rat, anaesthetized with urethane, are inhibited both by electrical stimulation of the ipsilateral caudate nucleus and by iontophoretically applied γ-aminobutyric acid (GABA). Iontophoretically applied picrotoxin reversibly blocks both of these inhibitory responses. These results are consistent with the hypothesis that GABA is the transmitter released by the inhibitory striato-nigral pathway.

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Picrotoxin antagonism of γ aminobutyric acid inhibitory responses and synaptic inhibition in the rat substantia nigra

Studies on the pharmacology of neurones in the nucleus accumbens of the rat.

1. The cyclic analogue of dopamine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) was injected into the lateral ventricle or bilaterally into the nucleus accumbens or caudate nucleus of conscious rats and its effect on locomotor activity was investigated. 2. When given intraventricularly, ADTN produced some stereotyped responses which were followed by a strong and long lasting stimulation of locomotor activity. When administered bilaterally into the nucleus accumbens a similar stimulation of locomotor activity was observed. ADTN had no effect on locomotor activity when injected bilaterally into the caudate nucleus. 3. The ADTN-induced locomotor stimulation following its intraventricular injection was completely abolished by a low dose of pimozide (0.01 mg/kg, i.p.) or haloperidol (0.5 mg/kg, i.p.). Pimozide (1 mg/kg, i.p.) given 30 min before ADTN injected bilaterally into the nucleus accumbens completely blocked locomotor stimulation. 4. Unilateral injections of ADTN (5 mug) into the nucleus accumbens caused locomotor stimulation but no turning. 5. Bilateral injections into the nucleus accumbens of 2-amino-6,7-dimethoxy-1,2,3,4-tetrahydronaphthalene or 0.9 percent w/v NaCl solution had no effect on locomotor activity. 6. It is concluded that the central stimulant action of ADTN is due to an effect on the dopamine receptors in the nucleus accumbens.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1975.tb07416.x

Geoffrey N. Woodruff

Papers

The action of substance P on mesencephalic reticular and substantia nigral neurones of the rat.

PRESYNAPTIC γ‐AMINOBUTYRIC ACID RECEPTORS IN THE RAT ANOCOCCYGEUS MUSCLE AND THEIR ANTAGONISM BY 5‐AMINOVALERIC ACID

Picrotoxin antagonism of γ aminobutyric acid inhibitory responses and synaptic inhibition in the rat substantia nigra

Studies on the pharmacology of neurones in the nucleus accumbens of the rat.

Studies on the behavioural pharmacology of a cyclic analogue of dopamine following its injection into the brains of conscious rats