Autoantibodies against opioid or glutamate receptors are associated with changes in morphine reward and physical dependence in mice

Capone, Francesca; Adriani, Walter; Shumilina, Maria; Izykenova, Galina A.; Granstrem, Oleg; Dambinova, Svetlana A.; Laviola, Giovanni

doi:10.1007/s00213-007-1062-y

Cited by 15 publications

(12 citation statements)

References 75 publications

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“…Such neuro-chemical sequel was consistently associated with a profile of behavioural modifications, including a rearrangement in patterns of nocturnal activity and diurnal resting, spontaneously expressed within home-cages settings. Such subtle effects in the wake-sleep rhythm were expected based on earlier data [49,55]: these effects are relevant, since they denote a longer and more intense beginning as well as an earlier end of the daily spontaneous activity in DAT-i mice. Interestingly, a considerable impairment of their adaptive capacity was found when considering choice behaviour in the delay-of-reward task contingencies.…”

Section: Discussionsupporting

confidence: 53%

“…Namely, the transient (but detectable) rise in circulating aAbs, generated by specific neuro-receptor fragments used as antigen, possibly together with a concomitantly permeable BBB (occasionally possible in stressful conditions; see [87]), might have generated persistent neuro-behavioural sequelae. Similarly, in a recent study [49], mice specifically immunized with fragments of glutamate receptors (GluR1) also demonstrated altered spontaneous activity and a stereotyped behavioural syndrome in response to a novelty-induced stress. A possible limitation in our study may be the lack of a further control group, immunized with a non-specific peptide.…”

Section: Discussionmentioning

confidence: 78%

“…Mice of batch II were monitored for spontaneous home-cage activity [49]. This was done thrice: 1, five days before immunization (baseline, PND 29–31); 2, after immunization (PND 42–44); 3, five days after the boost (PND 51–53).…”

Section: Methodsmentioning

confidence: 99%

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Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice

Adriani

Koot

Columba-Cabezas

et al. 2012

Behavioral and Brain Functions

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BackgroundPossible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype.MethodsMale CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec).ResultsDAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies.ConclusionsHyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro-behavioural alterations, coming along with an experimentally-induced rise of circulating DAT-directed aAbs, open the issue of a potential role for auto-immunity in vulnerability to impulse-control disorders.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 78%

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Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice

Adriani

Koot

Columba-Cabezas

et al. 2012

Behavioral and Brain Functions

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“…Indeed, germline THC exposure was associated with exacerbated stereotyped behavior in adult offspring during a period of acute opiate withdrawal (Contarino and Papaleo, 2005). Interestingly, chronic morphine exposure has been shown to induce stereotyped behaviors in mice, and this effect has been linked to disturbances in the regulation of glutamate receptors (Capone et al, 2008). Altogether, the observations presented in this study demonstrate that some of the molecular alterations induced by cross-generational effects of parental THC exposure might remain dormant, but can synergistically interact with environmental conditions directly experienced by F1 animals during their lifetime to alter individual vulnerability to psychiatric illnesses.…”

Section: Discussionmentioning

confidence: 99%

Parental THC Exposure Leads to Compulsive Heroin-Seeking and Altered Striatal Synaptic Plasticity in the Subsequent Generation

Szutorisz

DiNieri

Sweet

et al. 2014

Neuropsychopharmacol

173

154

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Recent attention has been focused on the long-term impact of cannabis exposure, for which experimental animal studies have validated causal relationships between neurobiological and behavioral alterations during the individual's lifetime. Here, we show that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, results in behavioral and neurobiological abnormalities in the subsequent generation of rats as a consequence of parental germline exposure to the drug. Adult F1 offspring that were themselves unexposed to THC displayed increased work effort to self-administer heroin, with enhanced stereotyped behaviors during the period of acute heroin withdrawal. On the molecular level, parental THC exposure was associated with changes in the mRNA expression of cannabinoid, dopamine, and glutamatergic receptor genes in the striatum, a key component of the neuronal circuitry mediating compulsive behaviors and reward sensitivity. Specifically, decreased mRNA and protein levels, as well as NMDA receptor binding were observed in the dorsal striatum of adult offspring as a consequence of germline THC exposure. Electrophysiologically, plasticity was altered at excitatory synapses of the striatal circuitry that is known to mediate compulsive and goal-directed behaviors. These findings demonstrate that parental history of germline THC exposure affects the molecular characteristics of the striatum, can impact offspring phenotype, and could possibly confer enhanced risk for psychiatric disorders in the subsequent generation.

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“…In a study, by GC/MS, S. cordifolium essential oil was characterized by a high content of sesquiterpenes, most of them oxygenated sesquiterpenes with curzerene (16.9%) and curzerenone (33.8%) as major constituent (4). According to some studies of the mechanisms involved in opioid tolerance and dependence, neurotransmitter systems such as nitric oxide (5), glutamate (6) dopamine (7), and receptors of stimulatory amino acids especially the glutamate receptors (NMDA) were of great importance. The role of NMDA has been proven in the opioid synaptic shaping process (8,9).…”

Section: Introductionmentioning

confidence: 99%

Effects of curzerene and Smyrnium cordifolium Boiss. extract on addiction withdrawal syndrome in mice

Nazari¹,

Yaghmaei²,

Rangin³

et al. 2018

J Herbmed Pharmacol

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Introduction: The purpose of this study was evaluating the effect of Smyrnium cordifolium extract (SCE) and curzerene (Cur) on withdrawal syndrome in mice compared with clonidine. Methods: High-performance liquid chromatography (HPLC) was used to determine the active ingredients of S. cordifolium. To evaluate the effects of SCE and Cur, 64 mice were divided into 8 equal groups. Groups 1, 2 and 3 were treated Cur (0.03, 0.06, 0.12 mg/kg, respectively). Groups 4, 5 and 6 were treated with SCE (100, 200, 300 mg/kg, respectively). The seventh group received just morphine. Group 8 received morphine and clonidine (0.2 mg/kg). Results: The results of this study showed that Cur was the most important ingredient in the extract of the plant, and the hydroalcoholic extract yield of S. cordifolium was 17.55% (w/w). The dose of 100 mg/kg of extract (SCE100) and 0.03 mg/kg curzerene (Cur1) (P < 0.05), dose of 200 mg/kg of extract (SCE200) and dose of 0.06 mg/kg curzerene (Cur2), (P < 0.01), dose of 300 mg/kg of extract (SCE300) and dose of 0.12 mg/kg of curzerene (Cur3) (P < 0.001) decreased the symptoms compared to clonidine. Doses higher than 300 mg/kg of extract and 0.12 mg/ kg of Cur had fatal effects. All doses of SCE and Cur in comparison with the control group at significant level (P < 0.001) reduced the number of jumping, rearing and teeth chattering in morphine-dependent mice. Conclusion: The findings suggest that SCE and Cur are capable of reducing the symptoms of withdrawal syndrome and their effectiveness may be more than clonidine in reducing the addiction withdrawal syndrome, which may have human therapeutic potential.

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Autoantibodies against opioid or glutamate receptors are associated with changes in morphine reward and physical dependence in mice

Cited by 15 publications

References 75 publications

Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice

Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice

Parental THC Exposure Leads to Compulsive Heroin-Seeking and Altered Striatal Synaptic Plasticity in the Subsequent Generation

Effects of curzerene and Smyrnium cordifolium Boiss. extract on addiction withdrawal syndrome in mice

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