Spinal modulation of the acoustic startle response: the role of norepinephrine, serotonin and dopamine

Astrachan, David I.; Davis, Michael T.

doi:10.1016/0006-8993(81)90121-9

Cited by 54 publications

(13 citation statements)

References 16 publications

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“…For example, intrathecal infusion of direct postsynaptic adrenergic agonists, including phenylephrine, have been found to increase startle responses in rats (Astrachan and Davis, 1981). Previous studies with cirazoline have shown that systemic administration of this a1 agonist can also increase startle responses, although at a higher dose range than what was utilized in the present studies (Carasso et al, 1998;Varty et al, 1999).…”

Section: Discussionmentioning

confidence: 50%

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Alsene

Carasso²,

Connors

et al. 2006

Neuropsychopharmacol

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Prepulse inhibition (PPI) refers to the attenuation of startle when a weak prestimulus precedes the startling stimulus. PPI is deficient in several psychiatric illnesses involving poor sensorimotor gating. Previous studies indicate that a1 adrenergic receptors regulate PPI, yet the extent to which these effects are mediated by central vs peripheral receptors is unclear. The present studies compared the effects of intracerebroventricular (ICV) vs intraperitoneal (IP) delivery of several a1 receptor agonists on PPI. Male Sprague-Dawley rats received either cirazoline (0, 10, 25, 50 mg/5 ml), methoxamine (0, 30, 100 mg/5 ml), or phenylephrine (0, 3, 10, 30 mg/5 ml) ICV immediately before testing. Separate groups received either cirazoline (0, 0.25, 0.50, 0.75 mg/kg), methoxamine (0, 2, 5, 10 mg/kg), or phenylephrine (0, 0.1, 2.0 mg/kg) IP 5 min before testing. PPI, baseline startle responses, and piloerection, an index of autonomic arousal, were measured. Cirazoline disrupted PPI; effective ICV doses were approximately six times lower than effective IP doses. Methoxamine disrupted PPI after ICV infusion but failed to affect PPI with IP doses that were up to 30-fold higher than the effective ICV dose. Phenylephrine disrupted PPI with ICV administration, but did not alter PPI after IP injection of even a 20-fold higher dose. None of the ICV treatments altered baseline startle magnitude, but phenylephrine and methoxamine lowered startle after administration of high systemic doses. Piloerection was induced by cirazoline via either route of administration, and by IP methoxamine and phenylephrine, but not by ICV infusion of methoxamine or phenylephrine. These findings indicate that a1 receptor-mediated PPI disruption occurs exclusively through stimulation of central receptors and is dissociable from alterations in baseline startle or autonomic effects.

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Section: Discussionmentioning

confidence: 50%

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Alsene

Carasso²,

Connors

et al. 2006

Neuropsychopharmacol

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“…A prominent modulatory role of central noradrenergic neurotransmission (and the descending coerulospinal system in particular) on the amplitude of the startle reflex is well established: bilateral 6-hydroxydopamine-induced lesions of the LC in rats lead to a significant reduction in startle (39) whereas intrathecal spinal injection of NE or an ␣ 1 -adrenergic agonist has the converse effect (51). Also, drugs specifically affecting the central noradrenergic neurotransmission modulate the amplitude of the acoustic startle, and this modulating effect can be abolished by lesioning the noradrenergic system, either in the entire CNS or specifically in the spinal cord (52).…”

Section: Discussionmentioning

confidence: 99%

Loss of locus coeruleus neurons and reduced startle in parkin null mice

Coelln

Thomas

Savitt

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

316

250

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Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized pathologically by degeneration of catecholaminergic neurons of the substantia nigra pars compacta and locus coeruleus, among other regions. Autosomalrecessive juvenile Parkinsonism (ARJP) is caused by mutations in the PARK2 gene coding for parkin and constitutes the most common familial form of PD. The majority of ARJP-associated parkin mutations are thought to be loss of function-mutations; however, the pathogenesis of ARJP remains poorly understood. Here, we report the generation of parkin null mice by targeted deletion of parkin exon 7. These mice show a loss of catecholaminergic neurons in the locus coeruleus and an accompanying loss of norepinephrine in discrete regions of the central nervous system. Moreover, there is a dramatic reduction of the norepinephrinedependent startle response. The nigrostriatal dopaminergic system does not show any impairment. This mouse model will help gain a better understanding of parkin function and the mechanisms underlying parkin-associated PD.

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“…Acute cocaine administration has been shown to increase levels of serotonin through reuptake blockade (Ritz et al 1990;Essman et al 1994;Cunningham et al 1996). Acute increases in 5-hydroxytryptamine (5HT) levels alone or via serotonergic agonists alter startle activity (Fechter 1974;Geyer et al 1975;Davis 1980;Johansson et al 1995), although serotonergic activity in the brain and the spinal cord may have opposite effects (Davis et al1980;Astrachan and Davis 1981;Davis et al 1986;Commissaris and Davis 1982). PPI is likewise sensitive to serotonergic stimulation (Mansbach et al 1989;Martinez and Geyer 1997;Padich et al 1996;Kehne et al 1996;Vollenweider et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Diminished Acoustic Startle in Chronic Cocaine Users

Efferen

Duncan

Szilágyi

et al. 2000

Neuropsychopharmacology

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Chronic cocaine use has been shown to produce neurochemical alterations which persist after acute withdrawal. This study assessed the effects of cocaine use on the acoustic startle response and sensorimotor gating using prepulse inhibition (PPI) Chronic cocaine use causes physiological and neurochemical alterations which persist well after drug cessation. At the commencement of abstinence, adaptive decreases in dopamine (DA) receptor density (Kleven et al. 1990;Laurier et al. 1994) and DA uptake (Izenwasser and Cox 1990), as well as increases in DA transporter (DAT) mRNA expression (Pilotte et al. 1994;Wamsley and Alburges 1993) and cocaine binding sites (Malison et al. 1998), have been reported. As abstinence continues, there are decreases in basal DA efflux (Parsons et al. 1991;Weiss et al. 1992), DAT mRNA expression (Pilotte et al. 1994), DAT in nucleus accumbens (Wilson et al. 1994), and D 1 receptor density (Kleven et al. 1990), leading to an overall state of decreased dopaminergic neurotransmission (Kuhar and Pilotte 1996).The acoustic startle response under observation in this study is a well characterized response consisting of a reflexive contraction of the skeletal musculature in response to an intense, abrupt stimulus. It is mediated by a simple 3-synapse subcortical circuit Koch et al. 1993). In humans, the response is quantified using electromyographic (EMG) measurements of the obicularis oculi facial muscle (Hoffman and Searle 1968). This response is sensitive to dopaminergic modulation. Direct and indirect DA agonists, such as apomorphine, cocaine and d-amphetamine, increase startle amplitude in animals (Kehne and Sorenson 1978;Davis 1980;Johansson et al. 1995), whereas DA antagonists such as haloperidol and clozapine reduce startle amplitude (Mansbach et al. 1988;Johansson et al. 1995 The acoustic startle response can be attenuated if a weak, non-startling prestimulus (a prepulse) immediately precedes the startle stimulus (Graham 1975;Braff et al. 1992). This phenomenon is known as prepulse inhibition of startle (PPI), the pharmacology of which has been well characterized in animal studies. Dopamine agonists, both direct and indirect, reduce or eliminate PPI; D2 antagonists reverse the effect of agonists such as apomorphine (Mansbach et al. 1988). On the other hand, D1 antagonism fails to reverse the effect (Swerdlow et al. 1991).The aim of the present study was to examine the functional consequences of long-term cocaine use by studying the acoustic startle response and PPI of the acoustic startle response during abstinence following prolonged cocaine use. MATERIALS AND METHODS SubjectsSixty cocaine subjects and 20 normal individuals were screened in consideration for participation. Nine healthy male normal controls and 15 male cocaine users were enrolled in the study after signing a VA/NYU IRB approved consent form.All subjects were screened to rule out presence or history of psychiatric or medical pathology (excluding substance induced disorders for the cocaine users) using the Structured Cli...

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Spinal modulation of the acoustic startle response: the role of norepinephrine, serotonin and dopamine

Cited by 54 publications

References 16 publications

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Loss of locus coeruleus neurons and reduced startle in parkin null mice

Diminished Acoustic Startle in Chronic Cocaine Users

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