Lobeline augments and inhibits cocaine-induced hyperactivity in rats

Polston, James E.; Cunningham, Colin S.; Rodvelt, Kelli R.; Miller, Dennis K.

doi:10.1016/j.lfs.2006.05.006

Cited by 24 publications

(24 citation statements)

References 27 publications

(44 reference statements)

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“…In contrast, operant performance for ICSS Another explanation for the impact of lobeline on PR responding for ICSS is that of general motoric impairment. This explanation, however, is not compelling given that acute administration of lobeline, at doses less than 3.0 mg/kg, does not alter locomotion in rats [16,28]. A final explanation for the present results is related to an aversive action of lobeline as suggested by the observation that lobeline will support a conditioned place aversion [29] and that lobeline, at 3.0 mg/kg, can support a conditioned taste aversion (CTA: [13]).…”

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confidence: 99%

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

Wellman

Elliott

Barbee

et al. 2008

Physiology & Behavior

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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.)...

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confidence: 99%

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

Wellman

Elliott

Barbee

et al. 2008

Physiology & Behavior

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“…This type of equipment was used in previous studies of lobeline's effects on locomotor behavior [14]. On two days prior to beginning of drug treatment, rats were injected (s.c.) with saline, placed in the monitor for 20 min, injected (i.p.)…”

Section: Drugsmentioning

confidence: 99%

“…Several preclinical studies have shown that lobeline reduces or blocks the in vitro and in vivo effects of abused psychostimulants [9][10][11][12][13][14]. In rat striatum, lobeline attenuated damphetamine-and nicotine-evoked dopamine release [12,13] and diminished methamphetamine-induced changes in dopamine storage [9] In behavioral studies, lobeline attenuates psychostimulant-induced activation in several rodent models of drug addiction (e.g., locomotor activity, drug discrimination and self-administration) [10,11,13,14].…”

Section: Introductionmentioning

confidence: 99%

“…In rat striatum, lobeline attenuated damphetamine-and nicotine-evoked dopamine release [12,13] and diminished methamphetamine-induced changes in dopamine storage [9] In behavioral studies, lobeline attenuates psychostimulant-induced activation in several rodent models of drug addiction (e.g., locomotor activity, drug discrimination and self-administration) [10,11,13,14]. For example, lobeline (0.3 -3 mg/kg) decreased methamphetamine selfadministration [10].…”

Section: Introductionmentioning

confidence: 99%

“…In locomotor activity studies in rats, lobeline (0.3 -3 mg/kg) attenuated cocaine-and nicotine induced hyperactivity after acute and repeated (12 days) stimulant treatment [11,14].…”

Section: Introductionmentioning

confidence: 99%

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