Increase in rat striatal extracellular dopamine and vacous chewing produced by two σ receptor ligands

Patrick, Saundra L.; Walker, J. Michael; Perkel, Jason M.; Lockwood, Michelle; Patrick, Robert L.

doi:10.1016/0014-2999(93)90456-r

Cited by 64 publications

(28 citation statements)

References 32 publications

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“…Further, the in vivo brain microdialysis technique has demonstrated that sigma ligands as (ϩ)-SKF-10,047 (Volonte et al 1995) and (ϩ)-pentazocine (Patrick et al 1993) increase the endogenous dopamine release in rat brain. In conclusion, we speculate that DHEAS and PREGS, as well as sigma 1 receptor agonists, reverse the reduction of dopamine release in the nucleus accumbens via activation of presynaptic sigma 1 receptors of the mesolimbic dopaminergic system and, as a result, conditioned fear stress response is attenuated.…”

Section: Discussionmentioning

confidence: 99%

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Noda

Kamei

et al. 2000

Neuropsychopharmacology

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Mice exhibited a marked suppression of motility (conditioned fear stress) when placed in an environment in which they had previously received an electric footshock. This conditioned fear stress response was dose-dependently attenuated by neurosteroids such as dehydroepiandrosterone sulfate (DHEAS; 25 and 50 mg/kg, s.c.) and pregnenolone sulfate (PREGS; s.c.), and by a putative sigma 1 047; 3 and 6 mg/kg, s.c.). However, progesterone (PROG; s.c.) and allopregnanolone (5 and 20 mg/kg, s.c.) had no effect on this stress response. The attenuating effects of DHEAS (50 mg/kg, s.c.), PREGS (50 mg/kg, s.c.), and ( ϩ )- 047 (6 mg/kg, s.c.) were reversed by i.p.), a sigma 1 receptor antagonist and PROG (5 or 10 mg/kg, i.p.). When DHEAS (25 mg/kg) was co-administered with ( ϩ )- 047 (3 mg/kg) Neurosteroids are synthesized in the brain, either de novo from cholesterol or from steroid hormone precursors, and accumulate in the nervous system to levels that are at least in part independent of steroidogenic gland secretion (Baulieu 1981). Neurosteroids, such as progesterone (PROG), pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their respective sulfate ester (PREGS or DHEAS), are involved in regulating the imbalance between excitation and inhibition in the CNS (Wu et al. 1991). The neurosteroids, allopregnanolone, allotetrahydrodeoxycorticosterone, PREGS, and DHEAS have been shown to possess antistress, anxiolytic, and antiamnesic properties in experimental animal models (Bitran et al. 1991;Brot et al. 1997;Maurice et al. , 1999Urani et al. 1998;Wieland et al. 1991). Recent evidence suggests that DHEAS and PREGS also play an important role in depression. Interestingly, decreased levels of DHEA, DHEAS, and PREGS have been associated with depression, cognitive dysfunction, aging, and other neurological conditions (Orentreich et al. 1984;Vallée et al. 1997), and DHEA improves the depression score in patients (Wolkowitz et al. 1997). However, the From the Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine (YN, HK, YK, TN, TN), Nagoya, Japan; and Department of Clinical Pharmacy, Faculty of Pharmacy, Meijo University (YK, TN, MN), Nagoya, Japan. receptor agonist, ( ϩ )-N-allylnormetazocine (( ϩ )-Address correspondence to: Dr. Toshitaka Nabeshima, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.Received October 18, 1999; revised February 2, 2000; accepted February 18, 2000. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 23 , NO . 3 Neurosteroids and Sigma 1 Receptors 277 mechanism underlying the beneficial effects of neurosteroids is not yet known.Neurosteroids have been shown to affect the activity of neurotransmitter systems, which are involved in a variety of neuropsychiatric illnesses. DHEAS and PREGS are negative allosteric modulators of the ␥ -aminobutyric acid (GABA) A receptors (Majewska 1992), and positive modulators of N-methyl-D-aspartate (NMDA) receptor-mediated res...

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Section: Discussionmentioning

confidence: 99%

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Noda

Kamei

et al. 2000

Neuropsychopharmacology

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“…DTG increased levels of striatal dopamine and dopamine metabolites between 40 and 120 min after injection (5,45). Although time points beyond 120 min were not examined, levels in most groups had begun to decline by this time point, making it unlikely that levels remained elevated 20 h postinjection.…”

Section: Discussionmentioning

confidence: 99%

The Delayed Effects of DTG and MK-801 on Latent Inhibition in a Conditioned Taste-Aversion Paradigm

Turgeon¹,

Auerbach²,

Duncan-Smith³

et al. 2000

Pharmacology Biochemistry and Behavior

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. The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste-aversion paradigm. PHARMACOL BIOCHEM BEHAV 66 (3) 533-539, 2000.-The delayed effects of phencyclidine (PCP) have been shown to disrupt latent inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to understand the mechanism of this disruption, the delayed effects of the selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA receptor antagonist MK-801 on latent inhibition were assessed in the same paradigm. Water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparing the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucrose consumed by animals in the PE group to the level observed in the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to produce a decrease in percent sucrose consumed in PE animals not treated with lithium chloride, indicating that the decrease observed in the LI paradigm could be due to MK-801-induced decrease in taste preference for sucrose rather than a disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste preference for sucrose did not significantly disrupt LI. None of the doses of DTG tested altered taste preference for sucrose. These data suggest a role for sigma receptors in the previously observed PCP-induced disruption of LI. LATENT inhibition (LI) is the impaired acquisition of a conditioned response to a stimulus that has been previously presented without reinforcement (35). LI is thought to be a measure of an organism's capacity to ignore irrelevant stimuli, and has been demonstrated in a variety of species including humans (4,35,36). Disruption of LI has been observed in nonmedicated acute schizophrenics (4) as well as animals and humans treated with the psychotomimetic drug amphetamine (14,22,49,(64)(65)(66)(67). Medicated schizophrenic patients do not demonstrate disrupted LI (4,37). In addition, antipsychotic medications reverse amphetamine-induced disruption of LI in animals (49,68), and can enhance LI on their own (11,15). These observations suggest that the disruption of LI is a useful animal model for this specific attentional deficit seen in schizophrenia (12,15). Phencyclidine (PCP) is a drug that can produce a psychotomimetic effect in humans (3,28,38) as well as a number of behavioral and cognitive changes in animals...

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“…Several previous studies suggested some dopaminergic activity induced by s 1 R agonists. For example increases in dopamine concentrations in striata of rats after administration of s 1 R agonists have been detected using in vivo Cocaine self-administration triggers sigma agonist reinforcement T Hiranita et al microdialysis (Gudelsky, 1995;Patrick et al, 1993). However, more recent studies examining the selective s 1 R agonist, PRE-084, indicated that it was significantly less potent than cocaine (Garcés-Ramírez et al, 2011), whereas the drugs PRE-084 and cocaine were equipotent in self-administration.…”

Section: Discussionmentioning

confidence: 99%

Self-Administration of Cocaine Induces Dopamine-Independent Self-Administration of Sigma Agonists

Hiranita

Mereu

Soto

et al. 2012

Neuropsychopharmacol

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Sigma 1 receptors (s 1 Rs) are intracellularly mobile chaperone proteins implicated in several disease processes, as well as psychiatric disorders and substance abuse. Here we report that although selective s 1 R agonists (PRE-084, ( þ )-pentazocine) lacked reinforcing effects in drug-naive rats, over the course of 28 experimental sessions, which was more than sufficient for acquisition of cocaine selfadministration, responding was not maintained by either s 1 R agonist. In contrast, after subjects self-administered cocaine s 1 R agonists were readily self-administered. The induced reinforcing effects were long lasting; a response for which subjects had no history of reinforcement was newly conditioned with both s 1 R agonists, extinguished when injections were discontinued, and reconditioned when s 1 R agonists again followed responses. Experience with food reinforcement was ineffective as an inducer of s 1 R agonist reinforcement. Although a variety of dopamine receptor antagonists blocked cocaine self-administration, consistent with its dopaminergic mechanism, PRE-084 self-administration was entirely insensitive to these drugs. Conversely, the sR antagonist, BD1063, blocked PRE-084 selfadministration but was inactive against cocaine. In microdialysis studies i.v. PRE-084 did not significantly stimulate dopamine at doses that were self-administered in rats either with or without a cocaine self-administration experience. The results indicate that cocaine experience induces reinforcing effects of previously inactive s 1 R agonists, and that the mechanism underlying these reinforcing effects is dopamine independent. It is further suggested that induced s 1 R mechanisms may have an essential role in treatment-resistant stimulant abuse, suggesting new approaches for the development of effective medications for stimulant abuse.

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Increase in rat striatal extracellular dopamine and vacous chewing produced by two σ receptor ligands

Cited by 64 publications

References 32 publications

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

The Delayed Effects of DTG and MK-801 on Latent Inhibition in a Conditioned Taste-Aversion Paradigm

Self-Administration of Cocaine Induces Dopamine-Independent Self-Administration of Sigma Agonists

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