Nullifying drug-induced sensitization: Behavioral and electrophysiological evaluations of dopaminergic and serotonergic ligands in methamphetamine-sensitized rats

McDaid, John; Tedford, Clark E.; Mackie, Alexander R; Dallimore, Jeanine E; Mickiewicz, Amanda L.; Shen, Fei; Angle, J.M.; Napier, T. Celeste

doi:10.1016/j.drugalcdep.2006.05.014

Cited by 30 publications

(43 citation statements)

References 71 publications

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“…By demonstrating that enhanced motor effects could be elicited for up to 2 weeks after repeated methamphetamine treatments, this experiment showed that the brain was in a persistently altered state. We have recently revealed that the behavioral sensitization induced by the methamphetamine treatment regimen used here does not reflect permanent damage, in that the behaviors can be reversed with postsensitization treatments with serotonergic and dopaminergic ligands (McDaid et al, 2006). Taken as a whole, these new findings validate the utility of the treatment/withdrawal protocol employed here for subsequent studies of the molecular processes that are associated with the capacity of rats to express enhanced responding to an acute methamphetamine challenge long after the sensitizing regimen is terminated.…”

Section: Discussionmentioning

confidence: 99%

“…These withdrawal times were selected based on the following electrophysiological studies in rats sensitized to psychostimulants: 1) neuronal activity in VTA and FCtx is altered at 3 days (but not after 14 days) of withdrawal (Wolf et al, 1993;White et al, 1995;Zhang et al, 1997;Peterson et al, 2000), and 2) in the NAc and VP, changes in spiking rates occur by 1 week of withdrawal and persist for up to 1 month (Henry and White, 1991;White et al, 1995;Brady et al, 2005;McDaid et al, 2006). Protocols Used for Evaluating Motor Responses to Methamphetamine.…”

Section: Methodsmentioning

confidence: 99%

“…Each of these regions projects to the ventral palladum (VP), and it is well known that the VP is an output regulator for limbic function (see Napier, 1993). We recently reported that sensitization to methamphetamine alters neuronal spiking in the VP (McDaid et al, 2006) and that sensitization to opiates alters VP expression of CREB and ⌬FosB (McDaid et al, 2005). The current study ascertained whether methamphetamine altered these signaling proteins in the VP.…”

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confidence: 99%

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Methamphetamine-Induced Sensitization Differentially Alters pCREB and ΔFosB throughout the Limbic Circuit of the Mammalian Brain

McDaid

Graham²,

Napier

2006

Mol Pharmacol

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Enhancements in behavior that accompany repeated, intermittent administration of abused drugs (sensitization) endure long after drug administration has ceased. Such persistence reflects changes in intracellular signaling cascades and associated gene transcription factors in brain regions that are engaged by abused drugs. This process is not characterized for the most potent psychomotor stimulant, methamphetamine. Using motor behavior as an index of brain state in rats, we verified that five once-daily injections of 2.5 mg/kg methamphetamine induced behavioral sensitization that was demonstrated (expressed) 3 and 14 days later. Using immunoblot procedures, limbic brain regions implicated in behavioral sensitization were assayed for extracellular signal-regulated kinase and its phosphorylated form (pERK/ERK, a signal transduction kinase), cAMP response element binding protein and its phosphorylated form (pCREB/CREB, a constitutively expressed transcriptional regulator), and ⌬FosB (a long-lasting transcription factor). pERK, ERK, and CREB levels were not changed for any region assayed. In the ventral tegmental area, pCREB and ⌬FosB also were not changed. pCREB (activated CREB) was elevated in the frontal cortex at 3 days withdrawal, but not at 14 days. pCREB levels were decreased at 14 days withdrawal in the nucleus accumbens and ventral pallidum. Accumbal and pallidal levels of ⌬FosB were increased at 3 days withdrawal, and this increase persisted to 14 days in the pallidum. Thus, only the ventral pallidum showed changes in molecular processes that consistently correlated with motor sensitization, revealing that this region may be associated with this enduring behavioral phenotype initiated by methamphetamine. The present findings expand our understanding of the neuroanatomical and molecular substrates that may play a role in the persistence of druginduced sensitization.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Methamphetamine-Induced Sensitization Differentially Alters pCREB and ΔFosB throughout the Limbic Circuit of the Mammalian Brain

McDaid

Graham²,

Napier

2006

Mol Pharmacol

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“…Moreover, agonists at these receptors attenuate cocaine-associated reinstatement (Grottick et al, 2000, Fletcher et al, 2002, Neisewander and Acosta, 2007, Burbassi and Cervo, 2008, Cunningham et al, 2011), self-administration (Grottick et al, 2000, Fletcher et al, 2002, Cunningham et al, 2011), as well as behavioral hyperactivity and sensitization (Grottick et al, 2000, Filip et al, 2004). 5-HT 2C Rs are constitutively active in rat brain (De Deurwaerdere et al, 2004), antagonists or inverse agonists with high affinity for 5-HT 2A/2C Rs nullify meth-induced neuronal sensitization (McDaid et al, 2007), and the putative 5-HT 2C R inverse agonist SB 206553 (SB206) reduces meth-seeking and meth-evoked motor activity (Graves and Napier, 2012). …”

Section: Introductionmentioning

confidence: 99%

Nucleus accumbens shell excitability is decreased by methamphetamine self-administration and increased by 5-HT2C receptor inverse agonism and agonism

et al. 2015

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Methamphetamine profoundly increases brain monoamines and is a widely abused psychostimulant. The effects of methamphetamine self-administration on neuron function are not known for the nucleus accumbens, a brain region involved in addictive behaviors, including drug-seeking. One therapeutic target showing preclinical promise at attenuating psychostimulant-seeking is 5-HT2C receptors; however, the effects of 5-HT2C receptor ligands on neuronal physiology are unclear. 5-HT2C receptor agonism decreases psychostimulant-mediated behaviors, and the putative 5-HT2C receptor inverse agonist, SB 206553, attenuates methamphetamine-seeking in rats. To ascertain the effects of methamphetamine, and 5-HT2C receptor inverse agonism and agonism, on neuronal function in the nucleus accumbens, we evaluated methamphetamine, SB 206553, and the 5-HT2C receptor agonist and Ro 60-0175, on neuronal excitability within the accumbens shell subregion using whole-cell current-clamp recordings in forebrain slices ex vivo. We reveal that methamphetamine self-administration decreased generation of evoked action potentials. In contrast, SB 206553 and Ro 60-0175 increased evoked spiking, effects that were prevented by the 5-HT2C receptor antagonist, SB 242084. We also assessed signaling mechanisms engaged by 5-HT2C receptors, and determined that accumbal 5-HT2C receptors stimulated Gq, but not Gi/o. These findings demonstrate that methamphetamine-induced decreases in excitability of neurons within the nucleus accumbens shell were abrogated by both 5-HT2C inverse agonism and agonism, and this effect likely involved activation of Gq–mediated signaling pathways.

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“…Ketanserin reduces behaviors by rats that are motivated by cocaine (Burmeister et al, 2004), nicotine (Levin et al, 2008) and methamphetamine (Bhatia et al, 2011), as well as neurophysiological effects of methamphetamine (McDaid et al, 2007). In studies of impulsivity, ketanserin reduces impulsive motor behavior (Passetti et al, 2003;Talpos et al, 2006;Fletcher et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats

Persons

Tedford

Celeste

2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Drug and behavioral addictions have overlapping features, e.g., both manifest preference for larger, albeit costlier, reinforcement options in cost/benefit decision-making tasks. Our prior work revealed that the mixed-function serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by abused drugs. To extend this work to behavioral addictions, here we determined if mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound, can alter decision-making in rats that is independent of drug (or food)-motivated reward. Accordingly, we developed a novel variable-ratio task in rats wherein intracranial self-stimulation was used as the positive reinforcer. Using lever pressing for various levels of brain stimulation, the operant task provided choices between a small brain stimulation current delivered on a fixed-ratio schedule (i.e., a predictable reward) and a large brain stimulation delivered following an unpredictable number of responses (i.e., a variable-ratio schedule). This task allowed for demonstration of individualized preference and detection of shifts in motivational influences during a pharmacological treatment. Once baseline preference was established, we determined that pretreatment with mirtazapine or ketanserin significantly decreased preference for the large reinforcer presented after gambling-like schedules of reinforcement. When the rats were tested the next day without drug, preference for the unpredictable large reinforcer option was restored. These data demonstrate that mirtazapine and ketanserin can reduce preference for larger, costlier reinforcement options, and illustrate the potential for these drugs to alter behavior.

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Nullifying drug-induced sensitization: Behavioral and electrophysiological evaluations of dopaminergic and serotonergic ligands in methamphetamine-sensitized rats

Cited by 30 publications

References 71 publications

Methamphetamine-Induced Sensitization Differentially Alters pCREB and ΔFosB throughout the Limbic Circuit of the Mammalian Brain

Methamphetamine-Induced Sensitization Differentially Alters pCREB and ΔFosB throughout the Limbic Circuit of the Mammalian Brain

Nucleus accumbens shell excitability is decreased by methamphetamine self-administration and increased by 5-HT2C receptor inverse agonism and agonism

Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats

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