Serotonin-2C and -2a receptor co-expression on cells in the rat medial prefrontal cortex.

Neural function within the medial prefrontal cortex (mPFC) regulates normal cognition, attention and impulse control, implicating neuroregulatory abnormalities within this region in mental dysfunction related to schizophrenia, depression and drug abuse. Both serotonin-2A (5-HT2A) and -2C (5-HT2C) receptors are known to be important in neuropsychiatric drug action and are distributed throughout the mPFC. However, their interactive role in serotonergic cortical regulation is poorly understood.

Striatal serotonin 2C receptors decrease nigrostriatal dopamine release by increasing GABA-A receptor tone in the substantia nigra.

Drugs acting at the serotonin-2C (5-HT2C) receptor subtype have shown promise as therapeutics in multiple syndromes including obesity, depression, and Parkinson's disease. While it is established that 5-HT2C receptor stimulation inhibits DA release, the neural circuits and the localization of the relevant 5-HT2C receptors remain unknown. This study used dual-probe in vivo microdialysis to investigate the relative contributions of 5-HT2C receptors localized in the rat substantia nigra (SN) and caudate-putamen (CP) in the control of nigrostriatal DA release.

The social defeat animal model of depression shows diminished levels of orexin in mesocortical regions of the dopamine system, and of dynorphin and orexin in the hypothalamus.

Anhedonia is a core symptom of clinical depression. Two brain neuropeptides that have been implicated in anhedonia symptomology in preclinical depression models are dynorphin and orexin; which are concentrated along lateral hypothalamic dopamine reward pathways. These affect regulating neuropeptides modulate each other's function, implicating an interactive dysfunction between them in anhedonia symptomology.

Chronic lithium treatment magnifies learning in rats.

Recent electrophysiological work shows that chronic lithium treatment increases long-term potentiation (LTP) in neurons of the hippocampus, and LTP is thought to be the major neurophysiological basis for the development of learning and memory. This suggests that lithium might enhance learning and memory. Available studies have mainly assessed memory using aversive conditioning paradigms, but very little is available on the effect of lithium on learning.

Prior morphine experience induces long-term increases in social interest and in appetitive behavior for natural reward.

Brain opioids regulate social emotional responsivity. One neuro-evolutionary theory of addiction suggests that exogenous opiates may induce addiction via opioid-controlled emotional changes; with the drug eventually fulfilling the need for social comfort that is normally provided by endogenous opioids. This view predicts that past opiate experience may enduringly alter social responsivity.

Evidence for the preferential involvement of 5-HT2A serotonin receptors in stress- and drug-induced dopamine release in the rat medial prefrontal cortex.

The mechanism(s) by which serotonin modulates dopamine release in the medial prefrontal cortex is not known, although studies suggest an involvement of 5-HT2 family receptors. We employed in vivo microdialysis and putatively selective 5-HT2A antagonists (M100907, MDL 11,939, SR46349B) to determine if 5-HT2A receptors are responsible for both drug- and stress-induced DA release in the medial prefrontal cortex. MDL 11,939 and SR46349B receptor-binding studies indicated, for the first time, that only MDL 11,939 had greater selectivity for the 5-HT2A vs the 5-HT2C receptor subtypes similar to M100907, and that both showed low or no affinity for non-5-HT2 receptors.

Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group.

Considerable evidence suggests that a dysfunction of the dopamine and serotonin (5-hydroxytryptamine or 5-HT) neurotransmitter systems contributes to a diverse range of pathological conditions including schizophrenia, depression and drug abuse. Recent electrophysiological and behavioral studies suggest that 5-HT modulates dopaminergic neurons in the ventral tegmental area via activation of 5-HT(2A) receptors. It is currently unknown if 5-HT(2A) receptors mediate their actions on dopaminergic neurons in the ventral tegmental area via direct or indirect mechanisms.

Chronic intermittent amphetamine pretreatment enhances future appetitive behavior for drug- and natural-reward: interaction with environmental variables.

Appetitive behavior for drug and sexual reward is enhanced in animals with a history of amphetamine-experience. The present experiment investigated whether prior exposure to a sensitizing regimen of amphetamine treatment would 'globally' enhance future appetitive behaviors of adult male Sprague-Dawley rats, and whether the drug preexposure-environment or intermittency of administration would affect this development. Reward appetite was compared in drug-experienced versus drug-naive rats using amphetamine place-preference conditioning (CPP) and a natural-incentive sensitization task, which measured appetitive approach for food and sexual reward.

Ethanol consumption and place-preference conditioning in the alcohol-preferring C57BL/6 mouse: relationship with motor activity patterns.

Ethanol place-preference conditioning (PC) was conducted in drug-naive and ethanol pre-exposed female and male C57BL/6J (C57) mice to assess whether environmental cues can develop positive incentive value for ethanol-preferring animals when associated with administration of ethanol. After 12 days episodic access to free-choice ethanol and/or water self-administration, mice received eight ethanol injections (1.75 g/kg/i.

Connections of the piriform cortex in homing pigeons (Columba livia) studied with fast blue and WGA-HRP.

The piriform cortex in homing pigeons receives a projection from the olfactory bulb and is necessary for the operation of those aspects of the navigational map based on olfactory stimuli in these animals. The afferent and efferent projections of the piriform cortex were studied using retrograde migration of wheat-germ agglutinin horseradish peroxidase (WGA-HRP) and Fast Blue, and anterograde migration of WGA-HRP. The piriform cortex was found to receive projections from, and send projections to, numerous regions and nuclei in the telencephalon, diencephalon and lower brainstem.

Cocaine and vigilance task performance of rats: effects of delay of reinforcement.

In two experiments rats were food-reinforced for pressing one of two levers in an operant chamber, with the correct lever being indicated by the position of a briefly illuminated light. In Experiment 1 the levers were always in the chamber, whereas in Experiment 2 the levers were inserted into the chamber immediately after cue light termination and withdrawn immediately after a choice response. The rats were tested under four conditions: after an injection (SC) of saline or 2.