The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties.
The effects of the dopamine (DA) receptor agonists apomorphine, bromocriptine and pergolide were compared with those produced by a DA receptor antagonist, haloperidol, in rats implanted with electrodes for chronic sleep recordings. Apomorphine (0.025-2.0 mg/kg) and bromocriptine (0.25-6.0 mg/kg) induced biphasic effects such that low doses decreased wakefulness (W) and increased slow wave sleep (SWS) and REM sleep (REMS), while large doses induced opposite effects. The effects of pergolide (0.05-0.5 mg/kg) on W and SWS were also biphasic, while REMS was suppressed over the range of dosages given. At 0.040 mg/kg, haloperidol increased W, while at 0.160 mg/kg it produced the opposite effect. Pretreatment with haloperidol (0.020 mg/kg) in a dose which preferentially acts at presynaptic sites reversed the effects of low doses of apomorphine, bromocriptine or pergolide on sleep and W. However, the compound differed substantially in its ability to block agonist effects. The increase in sleep after low doses of apomorphine, bromocriptine or pergolide could be related to activation of presynaptic D-2 receptors located on DA axons of mesolimbic and mesocortical systems. In addition, inhibition of norepinephrine and acetylcholine neurons having inhibitory D-2 receptors could contribute to the increase of sleep after small doses of the DA agonists.
Summary: A study was carried out on the effects of methoxamine, prazosin, and yohimbine on the sleep-wake cycle in rats prepared for chronic sleep recordings. Methoxamine (4-8 mg/kg), an al-adrenoceptor agonist, induced a doserelated increase in wakefulness (W) and a decrease in slow-wave sleep (SWS) and REM sleep (REMS). Prazosin (0.125-1 mg/kg), which selectively blocks aladrenoceptors, modified only slightly the amount of time spent in Wand SWS, and consistently decreased REMS values. Prazosin (0.5 mg/kg) reversed the effects of methoxamine, decreasing Wand increasing sleep. Yohimbine (3 mg/kg), which blocks a2-adrenoceptors, augmented Wand diminished sleep. Methoxamine (4 mg/kg) in animals pretreated with yohimbine (3 mg/kg) induced a further decrease of SWS and REMS and an increase of W Thus, pharmacological activation of al-or blocking of a2-adrenoceptors appears to decrease sleep and increase W Further, blocking of al-adrenoceptors decreases REMS. Rapid eye movement sleep depression by the aI-agonist or the aI-antagonist is tentatively ascribed to a critical change in noradrenergic transmission in the brain. Key Words:Waking-Sleep--Methoxamine-Prazosin-Yohimbine.Intraventricular administration of adrenergic agonists of al-and a2-adrenoceptors (norepinephrine, epinephrine) produces a state of prolonged wakefulness (W) (I). Compounds that indirectly activate both noradrenergic and dopaminergic receptors (amphetamine, methylphenidate) also profoundly affect the sleep-wake cycle. As a result, slow-wave sleep (SWS) and REM sleep (REMS) are decreased and W is increased (2,3). Several other compounds including methoxamine also induce an increase of waking electroencephalography (EEG), which has been related to selective activation of al-adrenoceptors (4).The present study quantifies the effect of methoxamine on the sleep-wake cycle of the rat and attempts to ascertain the role of al-and a2-receptors in the methoxamine-induced disruption of the sleep-wake cycle. The effects of methoxamine were assessed after pretreatment with either prazosin, which selectively blocks al-adrenoceptors, or yohimbine, which behaves as an antagonist of a2-adrenoceptors.
Childhood-onset schizophrenia is proposed to be associated with increased genetic loading compared with adult-onset schizophrenia because of its earlier age of onset and generally greater severity of symptoms. Diminished suppression of P50 auditory evoked responses to repeated stimuli and elevated anticipatory saccades during smooth pursuit eye movements are markers of genetic risk that are found in members of families with schizophrenia even in the absence of the full clinical disorder and appear to be transmitted in a single gene autosomal dominant fashion. Adult-onset schizophrenia is generally associated with one parent who demonstrates abnormal P50 sensory gating and elevated anticipatory saccades and one parent who is normal on the physiologic measures (i.e., unilineal inheritance). This study investigates whether childhood-onset schizophrenia is similarly unilineal or is associated with the inheritance of genetic risk factors from both parents (i.e., bilineal inheritance). Ten childhood-onset schizophrenic probands and their parents were studied. Their P50 sensory gating and anticipatory saccades were compared with adult-onset schizophrenic probands and their parents. Bilineality, measured as physiological impairment in both parents, occurred more frequently in childhood-onset probands than in adult-onset probands for both P50 sensory gating deficits (60% versus 13%) and elevated anticipatory saccades (60 versus 0%). Additionally, childhood-onset schizophrenic probands performed more poorly than adult-onset probands on the anticipatory saccade measure. This physiological evidence suggests that childhood-onset schizophrenia may be associated with increased genetic loading because of contributions of genetic risk from both parents.
Childhood-onset schizophrenia is proposed to be associated with increased genetic loading compared with adult-onset schizophrenia because of its earlier age of onset and generally greater severity of symptoms. Diminished suppression of P50 auditory evoked responses to repeated stimuli and elevated anticipatory saccades during smooth pursuit eye movements are markers of genetic risk that are found in members of families with schizophrenia even in the absence of the full clinical disorder and appear to be transmitted in a single gene autosomal dominant fashion. Adult-onset schizophrenia is generally associated with one parent who demonstrates abnormal P50 sensory gating and elevated anticipatory saccades and one parent who is normal on the physiologic measures (i.e., unilineal inheritance). This study investigates whether childhood-onset schizophrenia is similarly unilineal or is associated with the inheritance of genetic risk factors from both parents (i.e., bilineal inheritance). Ten childhood-onset schizophrenic probands and their parents were studied. Their P50 sensory gating and anticipatory saccades were compared with adult-onset schizophrenic probands and their parents. Bilineality, measured as physiological impairment in both parents, occurred more frequently in childhood-onset probands than in adult-onset probands for both P50 sensory gating deficits (60% versus 13%) and elevated anticipatory saccades (60 versus 0%). Additionally, childhood-onset schizophrenic probands performed more poorly than adult-onset probands on the anticipatory saccade measure. This physiological evidence suggests that childhood-onset schizophrenia may be associated with increased genetic loading because of contributions of genetic risk from both parents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.