Behavior and binding: Correlations between α1-adrenergic stimulation of acoustic startle and α1-adrenoceptor occupancy and number in rat lumbar spinal cord

Astrachan, David I.; Davis, Michael T.; Gallager, Dorothy W.

doi:10.1016/0006-8993(83)90765-5

Cited by 40 publications

(12 citation statements)

References 24 publications

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“…Concerning the implication of al-adrenoceptors in physiological functions of the NA system in the spinal cord, it has been reported that these receptors may participate in the regulation of blood pressure (Connor et al, 1981), antinociception (Howe et al, 1983), sympathetic nerve activity (Shi et al, 1988), various behavioral responses (Astrachan et al, 1983), and motor function (Mason and Fibiger, 1979). Our observed localization of al-adrenoceptors makes any interpretation related to functional aspects difficult, but is compatible with all these suggested actions.…”

Section: Discussionsupporting

confidence: 85%

Normal distribution of alpha‐1‐adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: A quantitative autoradiographic study

Roudet

Savasta

Feuerstein

1993

J of Neuroscience Research

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The distribution of alpha 1 (alpha 1)-adrenoceptors along the different segments of the spinal cord (cervical, thoracic, lumbar, and sacral) of normal rats has been studied by quantitative autoradiography using the specific alpha 1-antagonist [3H]Prazosin as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 1-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 1-adrenoceptor densities revealed a widespread distribution of these receptors along all segments of the spinal cord with a similar pattern in the various subregions of gray matter studied. This distribution of alpha 1-adrenoceptors was quite well correlated with the distribution of NA terminals, when referring to previous descriptions by immunohistochemistry. After 6-OHDA lesion, as well as caudally to the transection, a significant increase of alpha 1-adrenoceptor densities was observed in all spinal subregions thus evidencing supersensitivity. These results suggest that NA may act in the spinal cord, at least partly, via alpha 1-adrenoceptors and that the expression of these receptors could be influenced by NA dysfunction, as demonstrated here through the effects observed in lesioned animals.

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Section: Discussionsupporting

confidence: 85%

Normal distribution of alpha‐1‐adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: A quantitative autoradiographic study

Roudet

Savasta

Feuerstein

1993

J of Neuroscience Research

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“…Moreover, the effects of either LSD or mescaline can be blocked by 5-HT2 antagonists . It is possible that the excitatory effects of hallucinogens on startle could ultimately result from their actions on norepinephrine transmission, since norepinephrine appears to modulate startle (e.g., Adams and Geyer 1981;Astrachan et al 1983;Kehne and Davis 1985). Future studies looking at the effect of norepinephrine depletion on mescaline's excitatory effect on startle would be needed to test this possibility.…”

Section: Discussionmentioning

confidence: 99%

“…By themselves, most hallucinogens do not alter motorneuron excitability but they do increase the ability of 5-HT or NE to facilitate excitation produced by glutamate (McCall and Aghajanian 1980). Previous work has shown that NE or 5-HT (Davis et al 1980;Astrachan and Davis 1981) or NE or 5-HT agonists (Davis et al 1980;Astrachan and Davis 1981;Astrachan et al 1983;Davis et al 1986) increase startle amplitude after local infusion in the vicinity of the motorneurons in the spinal cord. Future studies looking at interactions between hallucinogens and intrathecal infusions of 5-HT or NE or their agonists, as well as the effects of 5-HT2 antagonists in this situation, could evaluate the role of these mechanisms in mediating the excitatory effects of hallucinogens on startle.…”

Section: Discussionmentioning

confidence: 99%

Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists

Davis

1987

Psychopharmacology

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The ability of serotonin2 (5-HT2) antagonists to block the excitatory effects of mescaline on the acoustic startle reflex were analyzed. Mescaline (20 mg/kg) caused a consistent increase in the amplitude of the acoustic startle reflex. This effect was blocked in a dose-related fashion by the 5-HT2 antagonist ritanserin (ED50 dose = 0.25 mg/kg IP). In contrast, even a high dose of ritanserin (2.0 mg/kg) did not block the excitatory effects of amphetamine on startle. Other 5-HT2 antagonists (ketanserin, cinanserin, LY 53857) also blocked mescaline's effect, whereas the 5-HT1 antagonist pindolol (5 mg/kg) did not. These results support the hypothesis that the behavioral effects of hallucinogens are mediated by agonist actions at 5-HT2 receptors.

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“…Increased NE transmission has long been known to enhance the magnitude of the involuntary startle response (Astrachan et al, 1983;Kehne and Davis, 1985). In recent years, the potential clinical importance of NE regulation of PPI has been underscored by the finding that prazosin, an a1 adrenergic receptor antagonist, recapitulates the behavioral effects of atypical but not traditional antipsychotics on PPI by preventing PPI deficits induced by the psychotomimetics phencyclidine (PCP) and dizocilpine Geyer, 1997, 1999).…”

Section: Introductionmentioning

confidence: 99%

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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Behavior and binding: Correlations between α1-adrenergic stimulation of acoustic startle and α1-adrenoceptor occupancy and number in rat lumbar spinal cord

Cited by 40 publications

References 24 publications

Normal distribution of alpha‐1‐adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: A quantitative autoradiographic study

Normal distribution of alpha‐1‐adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: A quantitative autoradiographic study

Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists

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

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