Modulatory effect of p-chlorophenylalanine microinjected into the dorsal and median raphe nuclei on cocaine-induced behaviour in the rat

Herges, Sonja; Taylor, David A.

doi:10.1016/s0014-2999(99)00333-7

Cited by 17 publications

(10 citation statements)

References 38 publications

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“…The samples were analyzed by ion exchange HPLC. The HPLC was coupled to an LC -4A amphometric detector and the height of the peaks was recorded using a chart recorder with peak heights determined manually (Herges and Taylor, 1999).…”

Section: Determination Of Striatal Dopamine Levelsmentioning

confidence: 99%

The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors

et al. 2001

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Factors that regulate terminal arbor size of substantia nigra pars compacta (SNpc) neurons during development and after injury are not well understood. This study examined the role of dopamine receptors in regulating arbor size. Terminal arbors were examined in mice with targeted deletion of the D1 or D2 dopamine receptor [D1(Ϫ/Ϫ) and D2(Ϫ/Ϫ) mice, respectively]. Terminal trees were also examined after treatment with receptor blockers and after partial SNpc lesions. Immunohistochemistry was performed, and the number of SNpc neurons and dopaminergic terminals in the striatum was estimated. The number of dopaminergic SNpc neurons were reduced in D1(Ϫ/Ϫ) and D2(Ϫ/Ϫ) mice. Density of dopaminergic terminals was unchanged in D1(Ϫ/Ϫ) mice and increased in D2 (Ϫ/Ϫ) mice. Steady-state striatal DA and DOPAC levels revealed that dopamine activity was enhanced in D2(Ϫ/Ϫ) mice but reduced in D1(Ϫ/Ϫ) mice.Two months after partial SNpc lesions, striatal terminal density was normal in both wild-type and D1(Ϫ/Ϫ) mice but reduced in D2(Ϫ/Ϫ) mice. Administration of DA receptor antagonists resulted in larger terminal arbors in D1(Ϫ/Ϫ) and wildtype mice, whereas D2(Ϫ/Ϫ) mice showed no change in terminal density.Functional blockade of the D2R during development or in the adult brain results in increased axonal sprouting. Partial SNpc lesions resulted in compensatory sprouting, only in mice with functional D2R. These results suggest that individual dopaminergic axons in D2(Ϫ/Ϫ) mice have reached maximal arbor size. We conclude that the D2 receptor may play a role in modulating the extent of the terminal arbor of SNpc neurons. Key words: regeneration; dopamine receptors; sprouting; axonal arbor; dopamine antagonists; D1 receptor knock-out; D2 receptor knock-out; 6-OHDA lesionsThere is now substantial evidence that neurons in the adult CNS can form new synapses, neurites, and branches (Raisman and Field, 1973;Fagan and Gage, 1994;Frotscher et al., 1997). After injury in the striatum or substantia nigra pars compacta (SNpc), a number of compensatory changes occur that suggest regenerative processes are present. These changes include the formation of new synaptic terminals, growth-cone structures (indicating axonal sprouting), neurite formation, increased number of tyrosine hydroxylase-immunoreactive (TH-IR) hypertrophic fibers penetrating the striatum, the upregulated expression of factors that support neurite outgrowth and cell survival, and increased dopamine levels (Zigmond et al

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Section: Determination Of Striatal Dopamine Levelsmentioning

confidence: 99%

The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors

et al. 2001

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“…Activation of the mesolimbic DA system, consisting of projections from the midbrain ventral tegmental area (VTA) to forebrain regions, including the nucleus accumbens (NAcc), is considered a critical event underlying the psychostimulant and reinforcing effects of cocaine (Wise, 1984). In general, activation of the serotonergic system appears to inhibit these effects of cocaine, whereas manipulations that decrease serotonergic transmission increase the psychostimulant and reinforcing properties of cocaine (Carroll et al, 1990;Loh and Roberts, 1990;Morrow and Roth, 1996;Herges and Taylor, 1999). Serotonergic neurons in the dorsal raphe project to the VTA and the NAcc (Azmitia and Segal, 1978;Herve et al, 1987;Van Bockstaele et al, 1994;Van Bockstaele et al, 1996) and influence dopaminergic transmission (Herve et al, 1979;Kelland et al, 1993;Prisco and Esposito, 1995;Brodie and Bunney, 1996), suggesting that regulation of mesolimbic dopaminergic activity may play an important role in the serotonergic modulation of cocaine effects.…”

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confidence: 99%

Enhanced Locomotor, Reinforcing, and Neurochemical Effects of Cocaine in Serotonin 5-Hydroxytryptamine 2C Receptor Mutant Mice

et al. 2002

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Brain serotonin [5-hydroxytryptamine (5-HT)] systems substantially influence the effects of cocaine; however, the contributions of individual 5-HT receptor subtypes to the regulation of cocaine responses are unclear. A line of mutant mice devoid of 5-HT2C receptors was used to examine the contribution of this receptor subtype to the serotonergic modulation of cocaine responses. Mutants display enhanced exploration of a novel environment and increased sensitivity to the locomotor stimulant effects of cocaine. In an operant intravenous self-administration model under a progressive ratio schedule of reinforcement, mutants display elevated levels of lever pressing for cocaine injections, indicating that the drug is more reinforcing in these mice. Moreover, mutants exhibit enhanced cocaine-induced elevations of dopamine (DA) levels in the nucleus accumbens, a brain region implicated in the stimulant and rewarding properties of cocaine. In contrast, phenotypic differences in dorsal striatal DA levels were not produced by cocaine treatment. These findings strongly implicate 5-HT2C receptors in the serotonergic suppression of DA-mediated behavioral responses to cocaine and as a potential therapeutic target for cocaine abuse.

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“…Indeed, an increasing number of behavioural studies suggest a modulatory role of 5-hydroxytryptamine (5-HT) on cocaineinduced locomotor activity in rodents. For example, pretreatment with the 5-HT biosynthesis inhibitor p-chlorophenylalanine enhanced the locomotor stimulatory properties of cocaine in rats, indicating an inhibitory role of 5-HT (ScheelKruÈ ger et al, 1977;Herges & Taylor, 1999a). It has been shown that this inhibitory e ect of the serotoninergic neurotransmitter system may be mediated by somatodendritic 5-HT 1A autoreceptors located in the dorsal raphe nucleus (Herges & Taylor, 1999b).…”

Section: Introductionmentioning

confidence: 99%

Involvement of 5‐HT₃ receptors in the nucleus accumbens in the potentiation of cocaine‐induced behaviours in the rat

Herges¹,

Taylor²

2000

British J Pharmacology

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1 The present study investigated the central e ects of the selective serotonin reuptake inhibitor (SSRI)¯uoxetine and the role of 5-hydroxytryptamine 3 (5-HT 3 ) receptors in the core of the nucleus accumbens (NAc) on cocaine-induced behavioural changes in rats. 2 The 5-HT 3 receptor antagonist ondansetron (1 or 10 ng) was microinjected bilaterally into the core of the NAc 60 min prior to peripheral cocaine (15 mg kg 71 , i.p.) administration followed by the assessment of locomotor activity, rearing activity and head bobs. Both doses of ondansetron attenuated cocaine's stimulatory e ect on behaviours. 3 Fluoxetine (0.05 or 5 mg) microinjected bilaterally into the core of the NAc 30 min before peripheral administration of cocaine produced dose-dependent biphasic e ects on cocaine-induced behaviours. Intra-NAc administration of 0.05 mg¯uoxetine resulted in a potentiation of cocaineinduced behaviours, while the higher dose of the SSRI (5 mg) attenuated the stimulant e ect of cocaine on behaviours. 4 To investigate a possible involvement of 5-HT 3 receptors in¯uoxetine's facilitatory action, ondansetron (10 ng) was microinjected 30 min prior to¯uoxetine (0.05 mg), which resulted in a signi®cant attenuation of the facilitatory e ect of¯uoxetine on cocaine-induced behaviours. 5 Thus, 5-HT 3 receptors in the core of the NAc appear to mediate stimulatory e ects on cocaineinduced locomotor activity, rears and head bobs, whereas the attenuation of cocaine-induced behaviours by¯uoxetine at the higher dose, suggests the involvement of a di erent 5-HT receptor subtype.

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Modulatory effect of p-chlorophenylalanine microinjected into the dorsal and median raphe nuclei on cocaine-induced behaviour in the rat

Cited by 17 publications

References 38 publications

The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors

The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors

Enhanced Locomotor, Reinforcing, and Neurochemical Effects of Cocaine in Serotonin 5-Hydroxytryptamine 2C Receptor Mutant Mice

Involvement of 5‐HT₃ receptors in the nucleus accumbens in the potentiation of cocaine‐induced behaviours in the rat

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Modulatory effect of p-chlorophenylalanine microinjected into the dorsal and median raphe nuclei on cocaine-induced behaviour in the rat

Cited by 17 publications

References 38 publications

The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors

The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors

Enhanced Locomotor, Reinforcing, and Neurochemical Effects of Cocaine in Serotonin 5-Hydroxytryptamine 2C Receptor Mutant Mice

Involvement of 5‐HT3 receptors in the nucleus accumbens in the potentiation of cocaine‐induced behaviours in the rat

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Involvement of 5‐HT₃ receptors in the nucleus accumbens in the potentiation of cocaine‐induced behaviours in the rat