Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways

Geyer, Mark A.; Puerto, A M; Dawsey, W J; Knapp, Suzanne; Bullard, W P; Mandell, Arnold J.

doi:10.1016/0006-8993(76)91023-4

Cited by 208 publications

(53 citation statements)

References 20 publications

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“…Injection of dopamine itself or dopamine agonists directly into the nucleus accumbens have been reported to stimulate locomotor activity in unrestrained animals (Costall et al, 1976;Pijnenburg et al, 1976). The nucleus accumbens, however, also receives 5-HTergic projections from the raphe nuclei (Conrad et al, 1974;Geyer et al, 1976). Lesioning of raphe nuclei produces hyperactivity (Costall et al, 1976;Geyer et al, 1976), which can be attenuated by 5-HT administration into the nucleus accumbens (Costall et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

“…The nucleus accumbens, however, also receives 5-HTergic projections from the raphe nuclei (Conrad et al, 1974;Geyer et al, 1976). Lesioning of raphe nuclei produces hyperactivity (Costall et al, 1976;Geyer et al, 1976), which can be attenuated by 5-HT administration into the nucleus accumbens (Costall et al, 1976). An inhibitory role of 5-HT on locomotor activity is further supported by the finding that dopamine-stimulated locomotor activity is attenuated by injecting 5-HT into the nucleus accumbens through the same cannula (Costall et al, 1976;Jones et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

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Long‐term imipramine treatment enhances locomotor and food intake suppressant effects of m‐chlorophenylpiperazine in rats

Aulakh

Cohen

Hill

et al. 1987

British J Pharmacology

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1 Administration of the 5-HTIB receptor agonist m-chlorophenylpiperazine (m-CPP) to rats produces dose-dependent decreases in locomotor activity and food intake. 2 The locomotor suppressant effect of m-CPP was inhibited by the 5-hydroxytryptaminergic antagonist, metergoline, but not by phentolamine, propranolol, clonidine, or haloperidol. 4 The food intake suppressant effects of m-CPP were enhanced following both short (3-5 days) and longer-term (21 days) treatment with imipramine. Rapidly developing 5-hydroxytryptamine uptake inhibition may be responsible for this change, or it may represent an earlier adaptive change in the 5-HTIB receptors mediating food intake compared to more complexly modulated motor responses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long‐term imipramine treatment enhances locomotor and food intake suppressant effects of m‐chlorophenylpiperazine in rats

Aulakh

Cohen

Hill

et al. 1987

British J Pharmacology

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“…The cell bodies and terminal regions of all three DA pathways are innervated by 5-HT neurons originating in the medial and dorsal raphe nuclei (Geyer et al, 1976;Parent et al, 1981;Beart and McDonald, 1982;Nedergaard et al, 1988). Studies show that there are direct synaptic contacts between 5-HT terminals and DA cells in the midbrain (Herve et al, 1987;Nedergaard et al, 1988).…”

Section: Da Systemsmentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

535

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…administration of a wide range of doses of CRF. The striatum was chosen because its 5-HT innervation derives solely from the dorsal raphe nucleus (Azmitia and Segal 1978;Geyer et al 1976;Vertes 1991). In addition, the effects of i.c.v.…”

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confidence: 99%

Effects of Corticotropin-Releasing Factor on Brain Serotonergic Activity

Price

Curtis

Kirby

et al. 1998

Neuropsychopharmacology

200

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The serotonergic dorsal raphe nucleus is innervated by corticotropin-releasing factor (CRF) and expresses CRF receptors, suggesting that endogenous CRF impacts on this system. The present study characterized interactions between CRF and the dorsal raphe serotonin (5-HT) system. The effects of intracerebroventricularly (i.c.v.) administered CRF on microdialysate concentrations of 5-HT in the lateralCorticotropin-releasing factor (CRF) is the hypothalamic neurohormone that initiates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary during stress (Vale et al. 1981). In addition, CRF is thought to function as a brain neurotransmitter that interacts with other neurotransmitter systems to coordinate autonomic and behavioral components of the stress response (Dunn and Berridge 1990;Owens and Nemeroff 1991;Valentino et al. 1993). This is supported by anatomical studies that have identified a widespread distribution of CRF-immunoreactive neurons and fibers outside of the hypothalamic-pituitary axis in brain regions that are not directly involved with endocrine responses to stress (Sakanaka et al. 1987;Swanson et al. 1983). This distribution far exceeds that required for CRF-evoked release of ACTH. Consistent with this widespread distribution of CRF-immunoreactive terminals, CRF receptor binding sites and CRF receptor mRNA are localized in diverse brain regions that are unrelated to their pituitary actions (Chalmers et al. 1995;De Souza 1987;Potter et al. 1994).Among the brain regions that are both innervated by CRF-immunoreactive fibers (Sakanaka et al. 1987;Swanson et al. 1983) and that contain mRNA for CRF receptors (Chalmers et al. 1995;Potter et al. 1994) are the dorsal and median raphe nuclei, the source nuclei of forebrain serotonergic innervation (Azmitia and Segal 1978;Kellar et al. 1977;Vertes 1991 dence for an impact of stress on forebrain 5-HT (Chaouloff 1993;De Souza and Van Loon 1986;Dunn 1988;Morgan et al. 1975;Pol et al. 1992;Tanaka et al. 1983), these anatomical findings lead to the speculation that CRF release within the raphe nucleus may mediate the effects of stress on this system. Nonetheless, there are few reports of the effects of CRF on measures of 5-HT function, and these have yielded equivocal results. For example, relatively high doses of CRF failed to alter levels of the 5-HT precursor, 5-hydroxytryptophan (Van Loon et al. 1982). Similarly, tissue levels of 5-HT or its catabolite 5-hydroxyindoleacetic acid (5-HIAA) were unaltered by CRF (Dunn and Berridge 1987). In contrast, CRF increased activity of tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of 5-HT, in cortex and midbrain (Singh et al. 1991), and 5-HIAA levels, measured by microdialysis, in hypothalamus and prefrontal cortex (Lavicky and Dunn 1993). Each of these studies used relatively indirect measures of 5-HT activity. A recent study, using in vivo microdialysis to measure extracellular 5-HT levels in the hippocampus of freely-moving rats, found no change after long term administration of ...

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Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways

Cited by 208 publications

References 20 publications

Long‐term imipramine treatment enhances locomotor and food intake suppressant effects of m‐chlorophenylpiperazine in rats

Long‐term imipramine treatment enhances locomotor and food intake suppressant effects of m‐chlorophenylpiperazine in rats

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Effects of Corticotropin-Releasing Factor on Brain Serotonergic Activity

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