Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those at nerve terminals regulate both synthesis and release. Considerable evidence has indicated that these are D 2 subtype receptors. However, many pharmacological studies have suggested an autoreceptor role for 3 receptor. This possibility was tested with mice lacking receptor as a result gene targeting. The basal firing rates within substantia nigra ventral...

The nucleus accumbens is a forebrain region that mediates cocaine self-administration and withdrawal effects in animal models of dependence. Considerable evidence suggests an important role dopamine D1 receptors these effects. Using combination current-clamp recordings brain slices whole-cell patch-clamp from freshly dissociated neurons, we found neurons are less excitable withdrawn rats because novel form plasticity: reduced sodium currents. Three days after discontinuation repeated...

Behavioral sensitization to psychomotor stimulants is accompanied by a number of alterations in the mesoaccumbens dopamine (DA) system, including DA autoreceptor subsensitivity ventral tegmental area (VTA) and D1 receptor supersensitivity nucleus accumbens (NAc). We investigated role excitatory amino acid (EAA) transmission induction cocaine these accompanying alterations. To do so, we used three glutamate antagonists, noncompetitive NMDA antagonist MK-801 (0.1 mg/kg), competitive CGS 19755...

Abstract Possible functional interactions between D1 and D2 dopamine (DA) receptors were examined using extracellular single‐cell recording with microiontophoretic application of selective receptor agonists both postsynaptically, in the rat nucleus accumbens (NAc) caudate‐putamen (CPu), presynaptically, at impulse‐regulating somatodendritic DA autoreceptors ventral tegmental area (A10) substantia nigra pars compacta (A9) In addition, synthesis‐modulating nerve terminal studied CPu NAc...

Drug-induced adaptations in the prefrontal cortex (PFC) contribute to several core aspects of addictive behaviors, but underlying neuronal processes remain essentially unknown. Here, we demonstrate that repeated vivo exposure cocaine persistently reduces voltage-gated K + current (VGKC) PFC pyramidal neurons, resulting enhanced membrane excitability. Analysis dopamine D 1 -class receptor (D R)-mediated modulation VGKC indicates that, despite absence direct R stimulation, downstream signaling...

Stable brain function relies on homeostatic maintenance of the functional output individual neurons. In general, neurons by converting synaptic input to as action potential firing. To determine mechanisms that balance this input–output/synapse–membrane interaction, we focused nucleus accumbens (NAc) and demonstrated a novel form synapse-to-membrane regulation, synapse-driven membrane plasticity ( h SMP). Through SMP, NAc adjusted their excitability functionally compensate for basal shifts in...

The medial prefrontal cortex (mPFC) plays a critical role in cocaine addiction. However, evidence to elucidate how the mPFC is functionally involved addiction remains incomplete. Recent studies have revealed that repeated administration induces various neuroadaptations pyramidal neurons, including reduction voltage-gated K + currents (VGKCs) and possible increase voltage-sensitive Ca 2+ ( I ). Here, we performed both current-clamp recordings brain slices voltage-clamp freshly dissociated...

The nucleus accumbens (NAc) is a forebrain area in the mesocorticolimbic dopamine (DA) system that regulates many aspects of drug addiction. Neuronal activity NAc modulated by different subtypes DA receptors. Although signaling has received considerable attention, mechanisms underlying D(2)-class receptor (D(2)R) modulation firing medium spiny neurons (MSNs) localized within remain ambiguous. In present study, we performed whole cell current-clamp recordings rat brain slices to determine...

Although the medial prefrontal cortex (mPFC) plays a critical role in cocaine addiction, effects of chronic on mPFC neurons remain poorly understood. Here, we performed visualized current-clamp recordings to determine repeated administration membrane excitability pyramidal rat brain slices. Following (15 mg/kg/day i.p. for 5 days) with 3-day withdrawal, alterations properties, including increased input resistance, reduced intensity intracellular injected currents required generation...

Emerging evidence suggests that cell senescence plays an important role in aging-associated diseases including neurodegenerative diseases. HIV leads to a spectrum of neurologic collectively termed HIV-associated neurocognitive disorders (HAND). Drug abuse, particularly methamphetamine (meth), is frequently abused psychostimulant among HIV+ individuals and its abuse exacerbates HAND. The mechanism by which meth lead brain dysregulation not entirely clear. In this study, we evaluated the...

Methamphetamine (Meth) is one of the most widely used illicit drugs worldwide, exerting potent psychostimulant effects that fuels its highly addictive nature. Chronic Meth use associated with severe cognitive impairments, particularly in executive functions, decision-making, and working memory, which persist long even after cessation use. These deficits are dysfunction glutamatergic pyramidal neurons medial prefrontal cortex (mPFC), regulates addiction cognition. Both human animal studies...

The nucleus accumbens (NAc) is an important forebrain area involved in sensitization, withdrawal effects, and self-administration of cocaine. However, little known about cocaine-induced alterations the neuronal excitability whole cell neuroplasticity this region that may affect behaviors. Our recent investigations have demonstrated repeated cocaine administration decreases voltage-sensitive sodium calcium currents (VSSCs VSCCs, respectively) freshly dissociated NAc neurons rats. In study,...

MK-801, a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) subtype of central glutamate receptor, stimulates locomotor activity in rats. Administration MK-801 (0.25mg/kg, i.p.) on four consecutive days results progressive sensitization its stimulatory effects. Because importance dopamine (DA) systems to other stimulants (e.g. amphetamine and cocaine), we examined possible role DA transmission sensitization. The D1 SCH 23390 was used for these experiments because well-established...

Dopamine (DA) modulation of excitability in medial prefrontal cortex (mPFC) pyramidal neurons has attracted considerable attention because the involvement mPFC DA several neuronal disorders. Here, we focused on inwardly rectifying K + current (IRKC) acutely dissociated from rat mPFC. A Cs -sensitive whole-cell IRKC was elicited by hyperpolarizing voltage steps a holding potential –50 mV. (20 μ m ) reduced amplitude, as did selective stimulation D 1 or 2 class receptors (D Rs and Rs)....

The nucleus accumbens (NAc) is intricately involved in maintaining cocaine self-administration. Cocaine inhibits the firing of most NAc cells due to its ability prevent reuptake dopamine (DA) and 5-hydroxytryptamine (5-HT), both which predominantly inhibit cell discharge vivo. present studies investigated roles DA 5-HT effects iontophoretically applied cocaine. Most exhibited negative/positive waveforms (Type I cells). These were significantly more sensitive than Type II (positive/negative...