Genesis of the Heroin-Induced Addictive Process: Articulation Between Psychodynamic and Neurobiological Theories.

Psychotherapeutic consultations of drug addict's patients in a Care, Support and Prevention Center in Addictology led us to propose several hypotheses on the genesis of addiction and its articulation with currently available neurobiological data. This care center dispenses both pharmacological maintenance medications for heroin dependence, such as methadone or buprenorphine, and psychological support. Our first hypothesis posits that the addictive process is driven by the narcissistic vulnerability of these patients, its neurobiological foundations being mainly mediated by the activation of endogenous opioid systems.

Protein kinase C inhibition rescues manic-like behaviors and hippocampal cell proliferation deficits in the sleep deprivation model of mania.

Background: Recent studies revealed that bipolar disorder may be associated with deficits of neuroplasticity. Additionally, accumulating evidence has implicated alterations of the intracellular signaling molecule protein kinase C (PKC) in mania.

Methods: Using sleep deprivation (SD) as an animal model of mania, this study aimed to examine the possible relationship between PKC and neuroplasticity in mania.

Astrocytes and gliotransmitters: new players in the treatment of major depression?

With a lifetime prevalence of more than 16% worldwide, major depressive disorder is one of the most common psychiatric disorders. Only one third of patients experience a complete therapeutic improvement with the use of current antidepressant drugs, with a therapeutic effect appearing only after several weeks of treatment. Hence, a better understanding of the mechanisms of action of current antidepressant treatments is needed to ultimately identify new targets and enhance beneficial effects.

Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats.

The neurobiological mechanisms underlying the pathophysiology and therapeutics of bipolar disorder are still unknown. In recent years, protein kinase C (PKC) has emerged as a potential key player in mania. To further investigate the role of this signaling system in mood regulation, we examined the effects of PKC modulators in behavioral tests modeling several facets of bipolar disorder and in adult hippocampal cell proliferation in rats.

A role for the PKC signaling system in the pathophysiology and treatment of mood disorders: involvement of a functional imbalance?

Mood disorders, such as bipolar and major depressive disorders, are frequent, severe, and often disabling neuropsychiatric diseases affecting millions of individuals worldwide. Available mood stabilizers and antidepressants remain unsatisfactory because of their delayed and partial therapeutic efficacy. Therefore, the development of targeted therapies, working more rapidly and being fully effective, is urgently needed.

Pharmacological blockade of 5-HT7 receptors as a putative fast acting antidepressant strategy.

Current antidepressants still display unsatisfactory efficacy and a delayed onset of therapeutic action. Here we show that the pharmacological blockade of serotonin 7 (5-HT(7)) receptors produced a faster antidepressant-like response than the commonly prescribed antidepressant fluoxetine. In the rat, the selective 5-HT(7) receptor antagonist SB-269970 counteracted the anxiogenic-like effect of fluoxetine in the open field and exerted an antidepressant-like effect in the forced swim test.

Therapeutic potential of 5-HT7 receptors in mood disorders.

Serotonin (5-HT) exerts its diverse physiological and pharmacological effects through the activation of multiple receptor subtypes. One of the newest members of this family is the 5-HT(7) receptor. Increasing investigations on this receptor are currently undertaken to highlight its physiological and physiopathological significance.

Changes in Proenkephalin mRNA expression in forebrain areas after amphetamine-induced behavioural sensitization.

Acute and repeated psychostimulant administration induces a long-lasting enhanced behavioural response to a subsequent drug challenge, known as behavioural sensitization. This phenomenon involves persistent neurophysiological adaptations, which may lead to drug addiction. Brain dopaminergic pathways have been implicated as the main neurobiological substrates of behavioural sensitization, although other neurotransmitters and neuromodulators may also participate.

Neurotensin receptor antagonist administered during cocaine withdrawal decreases locomotor sensitization and conditioned place preference.

Chronic use of psychostimulants induces enduringly increased responsiveness to a subsequent psychostimulant injection and sensitivity to drug-associated cues, contributing to drug craving and relapse. Neurotensin (NT), a neuropeptide functionally linked to dopaminergic neurons, was suggested to participate in these phenomena. We and others have reported that SR 48692, an NT receptor antagonist, given in pre- or co-treatments with cocaine or amphetamine, alters some behavioral effects of these drugs in rats.

Effects of the 5-HT7 receptor antagonist SB-269970 on rat hormonal and temperature responses to the 5-HT1A/7 receptor agonist 8-OH-DPAT.

The physiological function of 5-HT(7) receptors is not yet fully determined. This study was designed to characterize the involvement of 5-HT(7) receptor in rat body temperature regulation and in adrenocorticotropic hormone (ACTH) and corticosterone secretion. In the first part of our study, acute administration of SB-269970 (0.

Dopaminergic transmission in STOP null mice.

Neuroleptics are thought to exert their anti-psychotic effects by counteracting a hyper-dopaminergic transmission. Here, we have examined the dopaminergic status of STOP (stable tubule only polypeptide) null mice, which lack a microtubule-stabilizing protein and which display neuroleptic-sensitive behavioural disorders. Dopamine transmission was investigated using both behavioural analysis and measurements of dopamine efflux in different conditions.

Blockade of beta-adrenergic receptors prevents amphetamine-induced behavioural sensitization in rats: a putative role of the bed nucleus of the stria terminalis.

Recent findings have given evidence a role for noradrenergic transmission in the mechanisms underlying behavioural sensitization to psychostimulants. This work was undertaken to investigate the possible role of beta-adrenergic receptors in amphetamine-induced behavioural sensitization in rats. Rats were sensitized by a single administration of amphetamine (1 mg/kg s.

Endogenous neurotensin in the ventral tegmental area contributes to amphetamine behavioral sensitization.

Studies showing psychostimulant-like effects of exogenous neurotensin (NT) infused into the ventral tegmental area (VTA) prompted us to examine the role in the VTA of the endogenous NT in behavioral sensitization to amphetamine. Rats were sensitized to amphetamine by means of a subcutaneous amphetamine (1 mg/kg) injection, and the same dose was injected 7 days later to evaluate the expression of sensitization. The highly selective NT-receptor antagonist SR 142948A was injected into the VTA prior to the first and/or second amphetamine administration.

Long-term prenatal hypoxia alters maturation of brain catecholaminergic systems and motor behavior in rats.

In order to determine the influence of long-term prenatal hypoxia on the maturation of the brain catecholaminergic structures involved in motor and cognitive functions, pregnant rats were subjected to hypoxia (10% O2) from the 5th to 20th day of gestation. The in vivo activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was assessed, by accumulation of L-DOPA after i.p.

Chronic blockade of neurotensin receptors strongly reduces sensitized, but not acute, behavioral response to D-amphetamine.

This study investigated the effect of a chronic blockade of neurotensin (NT) receptors on the sensitized behavioral response to amphetamine using a nonpeptide NT receptor antagonist, SR 48692. Rats received four injections of D-amphetamine (0.5 or 1 mg/kg, IP) every other day (day 1, 3, 5 and 7) and were then challenged with the same dose of amphetamine after a 6-day withdrawal (day 14) to establish the presence of locomotor sensitization.