Chronic fluoxetine rescues changes in plasma membrane density of 5-HT1A autoreceptors and serotonin transporters in the olfactory bulbectomy rodent model of depression.

Reduced serotonin (5-HT) neurotransmission is postulated to underlie the pathogenesis of depression. The serotonin transporter (SERT) and 5-HT1A auto-receptors act in concert to ensure homeostasis of serotonin (5-HT) neurotransmission and regulation of their cell surface expression represent efficient mechanisms to maintain this homeostasis. Thus, we investigated the changes in the subcellular distribution of SERT and 5-HT1A receptors (5-HT1AR) in the rat olfactory bulbectomy model of depression using immuno-gold labeling and electron microscopy, and examined the effect of chronic treatment with the antidepressant, fluoxetine, a serotonin reuptake inhibitor, on the subcellular distribution of SERT and 5-HT1AR.

Role of the dorsal diencephalic conduction system in the brain reward circuitry.

Previous work with psychophysically based studies suggests that electrolytic lesion of the habenula, which lies in the dorsal diencephalic conduction system (DDC), degrades the intracranial self-stimulation (ICSS). This experiment was aimed at studying the importance of the DDC in brain stimulation reward, and its connections with other areas that support operant responding for brain stimulation. For this purpose, rats were implanted with stimulating electrodes at the dorsal raphe (DR) and lateral hypothalamus (LH), and lesioning electrodes in the medial forebrain bundle (MFB) and the DDC.

Differential contribution of mesoaccumbens and mesohabenular dopamine to intracranial self-stimulation.

The contribution of mesoaccumbens dopamine transmission to intracranial self-stimulation is well-established. However, although the nucleus accumbens comprises two main subregions, the shell and the core, little is known of the contribution of each to this behaviour. Our first aim was to study the effects of d-amphetamine infusions into the shell and core in order to understand their relative importance to reward and operant responding.

Individual phenotype predicts nicotine-haloperidol interaction in catalepsy: possible implication for the therapeutic efficacy of nicotine in Tourette's syndrome.

In individuals with Tourette's syndrome, the therapeutic efficacy of haloperidol can be augmented by nicotine. In laboratory rats, the dopamine antagonist haloperidol produces catalepsy and nicotine can potentiate it, although this effect is variable and not always observed. Our aim was to understand this variability.

Lesions of the lateral habenula dissociate the reward-enhancing and locomotor-stimulant effects of amphetamine.

Midbrain dopamine neurons play a key role in goal-directed behaviour as well as in some psychiatric disorders. Recent studies have provided electrophysiological, anatomical and biochemical evidence that the lateral habenula (LHb) exerts strong inhibitory control over midbrain dopamine neurons. However, the behavioural relevance of this inhibitory input is poorly understood.

Trafficking of neurokinin-1 receptors in serotonin neurons is controlled by substance P within the rat dorsal raphe nucleus.

Substance P (SP) modulates serotonin neurotransmission via neurokinin-1 receptors (NK1rs), and exerts regulatory effects on mood through habenular afferents to the dorsal raphe nucleus (DRN). We have previously demonstrated that, in the caudal DRN of rat, some serotonin neurons are endowed with NK1rs that are mostly cytoplasmic, whereas these receptors are mostly membrane bound in non-serotonin neurons. Here, we first examined by double-labeling immunocytochemistry the relationships between SP axon terminals and these two categories of DRN neurons.

Simultaneous anhedonia and exaggerated locomotor activation in an animal model of depression.

Rationale: Anhedonia, or hyposensitivity to normally pleasurable stimuli, is a cardinal symptom of depression. As such, reward circuitry may comprise a substrate with relevance to this symptom of depression.

Objectives: Our aim was to characterize in the rat changes in the rewarding properties of a pharmacological and a natural stimulus following olfactory bulbectomy (OBX), a pre-clinical animal model of depression.

Electrolytic lesions of the habenula attenuate brain stimulation reward.

The present experiment used electrolytic lesions in combination with curve-shift scaling to study the functional relation between the habenula and four different brain sites that support operant responding for brain stimulation reward. Rats were implanted with a monopolar stimulation electrode aimed at the lateral hypothalamus, ventral tegmental area, dorsal raphe or median raphe nuclei, and a lesioning electrode in the ipsilateral habenula. Operant nose poking resulted in self-administration of trains of electrical pulses to one of the above stimulation sites.

Intracranial self-stimulation of the dorsal raphe sensitizes psychostimulant locomotion.

The authors hypothesized that repeated rewarding electrical stimulation of the dorsal raphe can produce behavioral sensitization to psychostimulants. Groups of male rats were implanted with a stimulation electrode and preexposed to brain stimulation at parameters set to equate rewarding effectiveness across rats. Control groups were implanted with an electrode but never stimulated, or not implanted at all.

Mesencephalic substrate of reward: lesion effects.

Psychophysical studies suggest that reward-relevant neurons in the posterior mesencephalon (PM) form a caudal extension of the axonal pathway that mediates the rewarding effectiveness of electrical stimulation of the medial forebrain bundle. The present study sought to further characterize the reward-relevant functional link between these two regions by assessing changes to the rewarding effectiveness of caudal medial forebrain bundle stimulation (ventral tegmental area, VTA) subsequent to electrolytic lesions of different PM sites. A total of 13 rats were tested, 11 of these at bilateral VTA stimulation sites.

Mesencephalic substrate of reward: possible role for lateral pontine tegmental cells.

The present study was aimed at determining whether cells located in the lateral pontine tegmentum could constitute part of the neural circuitry that mediates the rewarding effect of mesencephalic electrical brain stimulation. Single action potentials were recorded from lateral pontine tegmental cells in urethane-anesthetized rats following antidromic activation from the ventral tegmental area and/or posterior mesencephalon. A total of 445 cells were recorded in 13 animals and of these, 44 were antidromically driven from the ventral tegmental area (n=13 ipsi-, n=5 contralateral), the posterior mesencephalon (n=8 ipsi-, n=5 midline), or from both sites (n=13).

Evidence for sequence-dependent and reversible nonspecific effects of PS-capped antisense treatment after intracerebral administration.

Phosphorothioate (PS)-capped phosphodiester (PE) oligodeoxynucleotides (ODNs) were used to determine whether the dopamine-dependent locomotor-stimulant effect of nicotine is mediated via a4 subunit-containing nicotinic receptors. To this end, rats received direct intraventral tegmental area infusion of a4 antisense via osmotic minipump, and their locomotor response to nicotine (0.2 mg/kg, s.