Lobeline, a potential pharmacotherapy for drug addiction, binds to μ opioid receptors and diminishes the effects of opioid receptor agonists

Miller, Dennis K.; Lever, John R.; Rodvelt, Kelli R.; Baskett, James A.; Will, Melissa L.; Kracke, George R.

doi:10.1016/j.drugalcdep.2007.02.003

Cited by 31 publications

(41 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggests that the lobeline (putative antagonist) inhibition was surmounted by increasing the morphine (agonist) dose, which is characteristic of pharmacological antagonism. This supports in vitro work suggesting lobeline is a µ opiate receptor antagonist [15].…”

Section: Discussionsupporting

confidence: 83%

“…It follows previous experiments where lobeline blocked the effects of opiate receptor agonists in vitro [15] and diminished heroin self-administration [16].…”

Section: Discussionsupporting

confidence: 82%

“…In that study, lobeline displaced D-Ala2, NME-Phe4, Gly5-ol-enkephalin (DAMGO) binding (Ki value ≈ 0.74 µM) in guinea pig brain homogenates, inhibited a DAMGO-induced potassium current in µ opiate receptors expressed in oocytes, and attenuated morphine-evoked dopamine release in rat striatum. Overall, these in vitro results [15] suggest that lobeline functions as a µ opiate receptor antagonist. Regarding the impact of lobeline on the behavioral effects of µ opiate receptor agonists, Hart and colleagues recently showed that lobeline (1 -3 mg/kg) decreased heroin (18 µg/kg/infusion) selfadministration in rats [16].…”

Section: Introductionmentioning

confidence: 66%

“…Recently, our laboratory demonstrated that lobeline diminishes the effects of µ opiate receptor agonists, possibly via an interaction with µ opiate receptors in brain [15]. In that study, lobeline displaced D-Ala2, NME-Phe4, Gly5-ol-enkephalin (DAMGO) binding (Ki value ≈ 0.74 µM) in guinea pig brain homogenates, inhibited a DAMGO-induced potassium current in µ opiate receptors expressed in oocytes, and attenuated morphine-evoked dopamine release in rat striatum.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lobeline Attenuates the Locomotor-Activating Properties of Repeated Morphine Treatment in Rats

Miller¹,

Polston²,

Rodvelt³

et al. 2011

Trop. J. Pharm Res

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 83%

“…It follows previous experiments where lobeline blocked the effects of opiate receptor agonists in vitro [15] and diminished heroin self-administration [16].…”

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lobeline Attenuates the Locomotor-Activating Properties of Repeated Morphine Treatment in Rats

Miller¹,

Polston²,

Rodvelt³

et al. 2011

Trop. J. Pharm Res

View full text Add to dashboard Cite

show abstract

“…In contrast, operant performance for ICSS in the present study was significantly altered by lobeline doses as low as 0.5 mg/kg. The mechanism of action by which lobeline alters reinforcement may be related to its effects on nicotinic receptors, opiate receptors [27] and vesicular dopamine transporters [16].…”

Section: Discussionmentioning

confidence: 99%

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Wellman

Elliott

Barbee

et al. 2008

Physiology & Behavior

View full text Add to dashboard Cite

The alkaloid lobeline inhibits the function of vesicular monoamine and dopamine transporters and diminishes the behavioral and neurochemical effects of nicotine and amphetamines. In the present study, we examined the interaction of systemic administration of lobeline on breakpoint scores on a progressive ratio (PR) schedule of intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB). Rats were run in two 30 min sessions, separated by a 10 min timeout period. At the end of the first session, each rat was injected with either 0, 0.5, 1.0 or 2.0 mg/kg (i.p.) lobeline. Positive controls known to suppress and to augment ICSS responding included the adrenergic antagonist prazosin (0, 0.5 and 2.0 mg/kg, i.p.) and the psychostimulant cocaine (0, 1.25, and 5.0 mg/kg, i.p.). Analyses of changes in average PR breakpoint scores between the 2 sessions revealed that lobeline significantly suppressed PR scores at doses of 0.5, 1.0 and 2.0 mg/kg, as did 0.5 mg/kg and 2.0 mg/ kg prazosin. These changes are unlikely to reflect motoric effects of these drugs inasmuch as neither lobeline nor prazosin alter locomotion at these doses. In contrast, PR breakpoint scores were significantly increased at 5.0 mg/kg cocaine, a dose that is sufficient to elevate locomotion in the rat. These results are consistent with the view that lobeline modulates brain reinforcement processes. Keywords Nicotinic receptors; Prazosin; CocaineMultiple behavioral assays can be used to index abuse potential [1][2][3] including the capacity of a drug to induce hyperlocomotion [4] and the capacity to induce conditioned place preference [5]. Rats will self-administer drugs such as cocaine or amphetamine into their vascular system [6]. Such drug infusions are thought to act on the neural substrates of reward. Electrodes placed along the path of the medial forebrain bundle (MFB) will support intracranial self-stimulation (ICSS) [7] and drugs of abuse are known to reduce the threshold current required to support ICSS [4,8,9]. Additionally, drugs of abuse are known to elevate progressive ratio (PR) responding for ICSS [10,11]. The latter types of studies are important in that a PR schedule, relative to a continuous reinforcement schedule, may be more sensitive to changes in reward engendered by neurotransmitter receptor antagonism [12].The alkaloid lobeline is derived from lobelia inflata [13]. Lobeline attenuates the hyperactivity induced by methamphetamine in rats and diminishes methamphetamine self-administration in rats [14][15][16]. The aforementioned results suggest that lobeline may function as a therapeutic tool for the treatment of methamphetamine abuse. Inasmuch as the impact of lobeline on ICSS responding has not been previously reported, the present study considered the impact of lobeline on breakpoints on a PR schedule of ICSS reinforcement. In this paradigm, the response requirement for reinforcement is increased systematically within a 30 min session [17]. Following completion of the first session, each rat was injected (i.p.)...

show abstract

References

2014

Drug Discovery for the Treatment of Addiction

View full text Add to dashboard Cite

Lobeline, a potential pharmacotherapy for drug addiction, binds to μ opioid receptors and diminishes the effects of opioid receptor agonists

Cited by 31 publications

References 32 publications

Lobeline Attenuates the Locomotor-Activating Properties of Repeated Morphine Treatment in Rats

Lobeline Attenuates the Locomotor-Activating Properties of Repeated Morphine Treatment in Rats

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

References

Contact Info

Product

Resources

About