Effects of corticosterone on excitatory amino acid responses in dopamine-sensitive neurons in the ventral tegmental area
Section snippets
Animals
Male hooded Lister rats (Bantin and Kingman, U.K.) were used throughout, of body weights between 200 and 270 g. Prior to slice preparation, the rats were housed, four per cage, at 21±1°C, with 55±10% relative humidity, and free access to tap water and laboratory rodent chow (CRM). Lighting was on a 12 h light/dark cycle, with the light phase between 09.00 to 21.00 and slices were prepared each day between 09.00 and 10.00.
Preparation of ventral tegmental area slices for electrophysiological recordings
The animals were killed by cervical dislocation. The skull was opened from
Effects of corticosterone on spontaneous firing and responses to dopamine
Corticosterone had no effect, at any of the concentrations (50 nM to 2 μM), on the spontaneous firing of dopamine-sensitive cells in the VTA (Fig. 1). The depression of firing rate produced by application of dopamine, 5 μM or 15 μM was also unaltered, by any of the corticosterone concentrations used.
Effects of corticosterone on the responses to excitatory amino acids
Corticosterone, at concentrations of 100 nM to 1 μM, significantly increased the responses to NMDA (Fig. 2a and b). The effects was seen with both concentrations of NMDA, 5 μM and 15 μM. No significant
Discussion
The results in this study demonstrated that corticosterone, at concentrations of 100 nM and above, potentiated the responses of VTA neurons to excitatory amino acids. These effects were quite specific, as no changes were seen in spontaneous firing or in the inhibitory effect of dopamine. The mineralocorticoid, aldosterone, did not show any potentiation of the responses to NMDA, while the glucocorticoid (Type II) receptor antagonist, RU38486, prevented the effect of corticosterone on the response
Conclusion
Effects such as we have reported here, of corticosterone on VTA neurons, could mediate the effects of stress in causing sensitization to drugs of abuse. The NMDA subtype of receptor is known to be involved in the development of sensitization. NMDA antagonists prevent the development of sensitization to amphetamine, cocaine and nicotine.13, 33The effect on amphetamine sensitization has been found to be produced by administration of an NMDA antagonist directly into the VTA,[13]providing good
Unlinked References
[3]is not cited in the text.[5]is not cited in the text.[18]is not cited in the text.[21]is not cited in the text.[22]is not cited in the text.[37]is not cited in the text.[42]is not cited in the text.
Acknowledgements
This work received financial support from the Medical Research Council, U.K.
References (42)
- et al.
A comparative study of self-administration of morphine into the amygdala and the ventral tegmental area in mice
Behav. Brain Res.
(1994) - et al.
Ethanol self-infusion into the ventral tegmental area by alcohol-preferring rats
Alcohol
(1994) - et al.
Control of neuronal excitability by corticosteroid hormones
Trends neurol. Sci.
(1992) - et al.
Induction, but not expression, of behavioural sensitisation to nicotine in the rat is dependent on glucocorticoids
Eur. J. Pharmac.
(1995) Neurotransmitter regulation of dopamine neurones in the ventral tegmental area
Brain Res. Rev.
(1993)- et al.
Nicotine-induced sensitisation to ambulant stimulant effect produced by daily administration into the ventral tegmental area and the nucleus accumbens in rats
Life Sci.
(1992) How far has molecular pharmacology contributed to our understanding of the mechanism(s) of general anaesthesia?
Pharmac. Ther.
(1996)- et al.
Stress-induced atrophy of apical dendrites of hippocampal CA3 neurones—involvement of glucocorticoid secretion and excitatory amino-acid receptors
Neuroscience
(1995) - et al.
Preferential occupation of mineralocorticoid receptors by corticosterone enhances glutamate-induced burst firing in rat midbrain dopaminergic neurones
Brain Res.
(1996) - et al.
Behavioural sensitisation to amphetamine is dependent on corticosterone receptor activation
Brain Res.
(1989)
Adrenal-steroid type-I and type-II receptor-binding—estimates of in vivo receptor number, occupancy, and activation with varying level of steroid
Brain Res.
Synergistic action of corticosterone on kainic acid-induced electrophysiological alterations in the hippocampus
Brain Res.
l-glutamate excitation of A10 dopamine neurones is preferentially mediated by activation of NMDA receptors; extra- and intracellular studies in brain slices
Brain Res.
Long- and short-term administration of corticosterone alters CA1 hippocampal properties
Neuroendocrinology
Chronic corticosterone treatment maintains synaptic activity of CA1 hippocampal pyramidal cells: acute high corticosterone administration increases action potential number
Synapse
Corticosterone impairs hippocampal neuronal calcium regulation
Brain Res.
Involvement of corticosterone in the modulation of ethanol consumption in the rat
Alcohol
Cortisol inhibition of calcium currents in guinea pig hippocampal CA1 neurones via G-protein-coupled activation of protein kinase C
J. Neurosci.
Membrane receptor-mediated electrophysiological effects of glucocorticoid on mammalian neurones
Endocrinology
Long-term control of neuronal excitability by corticosteroid hormones
J. steroid Biochem.
Involvement of N-methyl-d-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioural sensitisation to cocaine
J. Pharmac. exp. Ther.
Cited by (68)
Glucocorticoid regulation of lactate release from spinal astrocytes contributes to the induction of spinal LTP of C-fiber-evoked field potentials and the development of mechanical allodynia
2022, NeuropharmacologyCitation Excerpt :In addition, our results, which showed that adrenalectomy blocked HFS induced hypersensitivity, is consistent with a line of previous study showing that in adrenalectomized rats, nerve injury-induced neuropathic pain can be eliminated (Wang et al., 2004). Previous studies have shown that GR activation can potentiate NMDA-induced responses in dopamine sensitive neurons within the ventral tegmental area (Cho and Little, 1999), elevate intracellular Ca2+ concentration in hippocampal neurons (Takahashi et al., 2002), and mediate NMDA-induced neuronal degeneration in the rat magnocellular nucleus basalis (Abraham et al., 2000). These results suggest that neuronal GR have modulatory effects on the expression and function of NMDAR, which has been shown to be a critical factor in synaptic plasticity and chronic pain.
Glucocorticoids, metabolism and brain activity
2021, Neuroscience and Biobehavioral ReviewsNeuroendocrinology of reward in anorexia nervosa and bulimia nervosa: Beyond leptin and ghrelin
2019, Molecular and Cellular EndocrinologyNongenomic glucocorticoid effects and their mechanisms of action in vertebrates
2019, International Review of Cell and Molecular BiologyAcute social stress before the planning phase improves memory performance in a complex real life-related prospective memory task
2016, Neurobiology of Learning and MemoryCitation Excerpt :It is known that neural structures (i.e. ventral Striatum, frontal and medial PFC) and the dopaminergic pathways are involved in the reward system and are affected by stress (i.e. Barik et al., 2010; Czyrak & Chocyk, 2001; Diorio, Viau, & Meaney, 1993; Oswald et al., 2005). For instance, acute stress was found to enhance the efflux of dopamine in the ventral striatum, frontal and medial PFC (i.e. Barrot et al., 2000; Butts, Weinberg, Young, & Phillips, 2011; Cho & Little, 1999; Lataster et al., 2011). Certainly, research on the influence of acute stress on feedback-based learning behavior showed that acute stress had no effect on the accuracy of reward-dependent learning behavior.