Entry and distribution of hexamethonium in the central nervous system

Asghar, Khursheed; Roth, Lloyd J.

doi:10.1016/0006-2952(71)90189-4

Cited by 53 publications

(9 citation statements)

References 21 publications

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“…The exact nature of this inhibitory effect, however, will require further elucidation (see later discussion of activity with MPEP antagonism). Besheer et al (2004) found that the 0.4 mg/kg nicotine conditional stimulus was antagonized by the central and peripheral nicotinic acetylcholine receptor channel-blocking antagonist mecamylamine (Papke et al, 2001), and not by the predominately peripheral nicotinic acetylcholine receptor antagonist hexamethonium (Asghar and Roth, 1971), indicating that the cueing effects of nicotine were centrally mediated. Nicotinic acetylcholine receptors mediate release of both dopamine and glutamate in the mesocorticolimbic region of the brain (Pontieri et al, 1996 andSchilström et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

Murray

Bevins

2007

European Journal of Pharmacology

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Section: Discussionmentioning

confidence: 99%

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

Murray

Bevins

2007

European Journal of Pharmacology

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“…to freely moving rats [32], In that report, it was demonstrated that systemic nicotine released NE in the PVN by a dose-dependent, Mec-sensitive mechanism. In contrast, peripherally administered hexamethonium, a quartenary amine which penetrates the blood-brain barrier poorly [33], was ineffective in blocking nicotine-stimulated NE secretion in the PVN. The current studies were conducted to determine the effect of the direct administration of nicotine into the IVth ventricle (intracerebroventricularly, i.c.v.…”

Section: Introductionmentioning

confidence: 85%

Nicotinic Agonists Administered into the Fourth Ventricle Stimulate Norepinephrine Secretion in the Hypothalamic Paraventricular Nucleus: An in vivo Microdialysis Study

et al. 1995

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Nicotinic cholinergic agonists stimulate ACTH secretion by a central mechanism involving brainstem catecholamines. In vivo microdialysis studies were conducted to measure the release of norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) in response to the administration of nicotine (Nic) or another nicotinic cholinergic (NAch) agonist, cytisine (Cyt), directly into the IVth ventricle. Alert, freely mobile rats, equipped 24 h previously with a chronic guide cannula in the IVth ventricle and microdialysis probe in the PVN, were injected with artificial cerebrospinal fluid (CSF, 500 nl/60 s), Nic (1–5 µg), or Cyt (1–25 µg) after three 20-min baseline samples had been taken. Analysis of the dialysates by HPLC with electrochemical detection demonstrated the dose-dependent secretion of PVN NE to Nic or Cyt with ED₅₀s of approximately 1 or 6 µg, respectively; these were completely blocked by prior IVth ventricular injection of the NAch antagonist, mecamylamine (4 µg). In contrast, α-bungarotoxin, which antagonizes the action of NAch agonists by acting through the α₇bungarotoxin-type NAchR, failed to reduce the NE response to Nic. Partial, but significant desensitization of NE secretion in response to a second injection of Nic (2.5 or 5 µg) 100 min after the first was seen, whereas NE responses to the second injection of Cyt (5 or 25 µg) were completely desensitized. However, cross-desensitization of each agonist to the other did not occur. This may reflect heterogeneity of the NAch receptor subtypes involved. The results of this study establish a correlation between the action of nicotine on brainstem norepineph-rinergic regions and the resultant release of NE in the PVN, which would lead to the release of ACTH secretagogues.

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“…On the fi fth day of the cycle, each rat was pretreated s.c. with saline, the central and peripheral nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine [(0.5 or 1.0 mg/kg); see Martin et al 1989], or the peripheral nAChR antagonist hexamethonium [(2.5 mg/kg or 5.0 mg/kg); see Asghar and Roth 1971] 15 min before nicotine (i.e., 20 min before start of the test session). Rats were tested twice at each condition and nicotine (0.4 mg/kg) was administered 5 min before placement in the chambers (cf.…”

Section: Group 3: Nachr Antagonismmentioning

confidence: 99%

Nicotine as a signal for the presence or absence of sucrose reward: a Pavlovian drug appetitive conditioning preparation in rats

et al. 2004

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Abstract:Rationale: In Pavlovian conditioning research, nicotine is typically conceptualized as the unconditioned stimulus (US) that becomes associated with an exteroceptive conditioned stimulus (CS). This research has not explored the possibility that nicotine can also function as a CS. Objectives: The present research examined whether nicotine served as a CS for the presence (CS+) or absence (CS-) of sucrose and started defi ning its specifi city. Methods and results: Rats trained in the CS+ condition had nicotine (0.4 mg/ kg, base) paired intermittently with brief access to sucrose. Intermixed were saline sessions without sucrose. Nicotine acquired the ability to evoke goal tracking. This conditioned response (CR) decreased across extinction sessions. The CR was sensitive to nicotine dose (ED 50 =0.113 mg/kg) and administration to testing interval; 0-min and 100-min delays produced no CR. The CS properties were specifi c to nicotine in that amphetamine and bupropion substitution was incomplete. Rats in the CS-condition received similar discrimination training except that sucrose was paired with saline. Nicotine also served as a CS-; the saline state CS+ acquired control of goal tracking. Mecamylamine, but not hexamethonium, blocked nicotine's ability to serve as a CS+ and CS-, indicating a role for central nicotinic acetylcholine receptors. Conclusions: Nicotine served as a signal for the presence or absence of sucrose. The extinction, CS-, and substitution results eliminated a psycho motor stimulant account. The conceptualization of nicotine as a CS suggests novel empirical research in which a drug acquires additional inhibitory and/ or excitatory value based on other outcomes present during its effects.

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Entry and distribution of hexamethonium in the central nervous system

Cited by 53 publications

References 21 publications

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

Nicotinic Agonists Administered into the Fourth Ventricle Stimulate Norepinephrine Secretion in the Hypothalamic Paraventricular Nucleus: An in vivo Microdialysis Study

Nicotine as a signal for the presence or absence of sucrose reward: a Pavlovian drug appetitive conditioning preparation in rats

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