Poor sensitization of 50-kHz vocalization response to amphetamine predicts rat susceptibility to self-administration of the drug.

Rationale: Our previous studies showed promise for using sensitization of the frequency-modulated 50-kHz vocalization response to amphetamine (AMPH) as an index of rat vulnerability to AMPH addiction.

Objective: This study aimed to test the utility of sensitizing frequency-modulated (FM) 50-kHz vocalization in the AMPH self-administration paradigm as well as the ability of N-acetylcysteine to prevent self-administration relapse.

Methods: Rats were subjected to the so-called two-injection protocol of sensitization (TIPS) using AMPH and were categorized as low-sensitized callers (LCTIPS) or high-sensitized callers (HCTIPS) based on the individual outcomes.

Novel candidate genes for alcoholism--transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of Warsaw alcohol-preferring and non-preferring rats.

Objective: Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain functions, including reward system and addiction. The current study aimed to identify genes that may underlie differential ethanol preference in Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats.

Neonatal serotonin (5-HT) depletion does not affect spatial learning and memory in rats.

Background: Extensive previous research has suggested a role for serotonin (5-HT) in learning and memory processes, both in healthy individuals and pathological disorders including depression, autism and schizophrenia, most of which have a developmental onset. Since 5-HT dysfunction in brain development may be involved in disease etiology, the present investigation assessed the effects of neonatal 5-HT depletion on spatial learning and memory in the Morris water maze (MWM).

Methods: Three days old Sprague-Dawley rats were pretreated with desipramine (20 mg/kg) followed by an intraventricular injection of the selective 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 70 μg).

Neonatal serotonin (5-HT) depletion does not disrupt prepulse inhibition of the startle response in rats.

The neurodevelopmental hypothesis of many brain disorders is based on the notion that environmental factors have significant effects on brain maturation. Because serotonin (5-HT) dysfunction in development may be involved in disease etiology, the present investigation assessed the effects of neonatal 5-HT depletion on prepulse inhibition of the startle response (PPI) in rats. Three-day-old Sprague-Dawley rats were pretreated with desipramine (20 mg/kg), followed by an intraventricular injection of the selective 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 70 μg dissolved in 2 μl of 0.

The influence of neonatal serotonin depletion on emotional and exploratory behaviours in rats.

Recent studies have shown that neurodevelopmental disturbances in the structure and function of the brain are significant factors in the onset of psychiatric disorders. Such deficits may also affect neurotransmission. Among the different neurotransmitter systems, serotonin (5-HT) plays an important role in the organisation and maturation of brain structures during development.

Effect of varenicline on the acute and repeated locomotor responses to nicotine in rats.

The objective of this study was to evaluate the efficacy of varenicline, a novel partial agonist at alpha 4 beta 2 and full agonist at alpha 7 nicotinic acetylcholine receptor (nAChR) subtypes, in blocking the locomotor effects of acute or repeated treatments with nicotine (0.4 mg/kg, s.c.

Active versus passive cocaine administration: differences in the neuroadaptive changes in the brain dopaminergic system.

There is considerable evidence that chronic exposure to cocaine is associated with low striatal dopamine D2 receptor availability. In the present study we wished to determine whether neuroadaptive changes in densities of D2 receptors were due to direct pharmacological actions of cocaine or they reflected motivational states that were present when cocaine injection depended on active drug-seeking behavior and whether these changes were related to the actual expression of D2 mRNA. To achieve this goal we utilized a "yoked" procedure in which rats were tested simultaneously in groups of three, with only one rat actively self-administering cocaine while the other two received yoked injections of either cocaine or saline.

History of cocaine self-administration alters morphine reinforcement in the rat.

It has been shown repeatedly that cocaine pre-exposure may sensitise neurochemical and behavioural responses to opioid drugs. The aim of the present study was to investigate effects of a prior history of cocaine self-administration on morphine reinforcement in the rat. Male Sprague-Dawley rats were allowed to acquire intravenous cocaine self-administration (0.

Cycloheximide impairs acquisition but not extinction of cocaine self-administration.

The aim of the present study was to assess the role of de novo protein synthesis in the acquisition and extinction of cocaine self-administration. In a first experiment, rats were trained to respond for intravenous cocaine infusions (0.3 mg/kg) and a protein synthesis inhibitor, cycloheximide (CHX; 3 mg/kg, s.

Contingency does not contribute to the effects of cocaine self-administration on prodynorphin and proenkephalin gene expression in the rat forebrain.

Neuroadaptations in the brain opioid systems produced by chronic exposure to drugs of abuse may contribute to the drug dependence and addiction. Although regulation of the gene expression of the opioid propeptides proenkephalin (PENK) and prodynorphin (PDYN) by psychostimulants has previously been described, little attention has been paid to dissociating effects of pharmacological actions of the drugs from those produced by motivational processes driving active drug intake in self-administration paradigms. In the present study, effects of response-dependent (contingent) and response-independent (noncontingent) cocaine administration on the PENK and PDYN gene expression in the rat forebrain have been directly compared using the "yoked" self-administration procedure.

Metabolic transformation plays a primary role in the psychostimulant-like discriminative-stimulus effects of selegiline [(R)-(-)-deprenyl].

l-Deprenyl [selegiline, (R)-(-)-deprenyl] is a selective inhibitor of monoamine oxidase B (MAO-B) used in the treatment of Parkinson's disease and proposed as an antidepressant and an aid for cigarette-smoking cessation and treatment of psychostimulant abuse. Beneficial therapeutic effects of (R)-(-)-deprenyl may also result from indirect actions. Brain levels of dopamine and beta-phenylethylamine (beta-PEA), a behaviorally active endogenous trace amine, increase after (R)-(-)-deprenyl treatment due to MAO-B blockade and (R)-(-)-deprenyl is metabolized to (R)-(-)-methamphetamine and (R)-(-)-amphetamine, suggesting that (R)-(-)-deprenyl may have psychostimulant-like behavioral effects.

Sigma1 receptor upregulation after chronic methamphetamine self-administration in rats: a study with yoked controls.

Rationale: Sigma(1) receptors (Sig-1R) are implicated in behavioral sensitization, conditioned place preference, and cellular restructuring induced by psychostimulants. We previously reported that rats which actively self-administered methamphetamine for 5 weeks and were then withdrawn from methamphetamine for 24 h showed downregulation of dopamine D(2) autoreceptors (approximately 30%) in the midbrain and this was not seen in rats that passively received injections of methamphetamine or saline at the same time (yoked controls). Involvement of Sig-1R in the self-administration of psychostimulants, however, has never been reported.

Intravenous self-administration of morphine and cocaine: a comparative study.

The aim of the present study was to estimate differences between patterns of morphine and cocaine use in Sprague-Dawley rats. This was done by first developing a set of conditions under which both drugs would be consistently self-administered over time. Subsequently rats were studied in groups of three, with only one rat actively self-administering morphine or cocaine while others two receiving yoked injections of either the drug or saline.

Ethanol-reinforced behaviour predicts acquisition but not extinction of cocaine self-administration in the rat.

Aims: The aim of the present study was to evaluate the relationship between operant oral ethanol self-administration and intravenous (i.v.) cocaine self-administration in male Wistar rats.

Lack of persistent changes in the dopaminergic system of rats withdrawn from methamphetamine self-administration.

A continuing challenge for studies in the neurobiology of drug abuse is to identify and characterize long-lived neuroadaptations that can trigger craving and relapse. We previously reported that rats that had actively self-administered methamphetamine for 5 weeks and were then withdrawn from methamphetamine for 24 h showed marked decreases in somatodendritic dopamine D(2) autoreceptor levels in the ventral tegmental area and median and dorsal part of the substantia nigra zona compacta with a corresponding down-regulation of dopamine D(1) receptors in the shell of the nucleus accumbens. The purpose of the present study was to determine whether neuroadaptive changes in dopamine receptors or transporters in the brains of rats withdrawn for 24 h from chronic methamphetamine self-administration are persistent changes that can be demonstrated long after withdrawal.