Activation of Protein Kinase C Modulates Light Responses in Horizontal Cells of the Turtle Retina

The effect of phorbol esters on the light-evoked responses of horizontal cells were studied in the turtle eyecup preparation. Phorbol esters caused a reduction in receptive field size and a significant decrease in the amplitude of responses to annular and full-field illumination; however, they caused only minor changes in responses to small spots in the receptive field centre. The dark membrane potential was not affected. The results suggest that phorbol esters may affect both coupling resistance and membrane resistance in horizontal cells. The effects of phorbol esters were blocked by the protein kinase C inhibitor staurosporine, and inactive phorbol ester had no effect, making it very likely that the phorbol ester effects were mediated through activation of protein kinase C. The above effects of the phorbol esters were considerably reduced by the dopamine antagonists haloperidol and fluphenazine, suggesting that they were in part mediated by release of dopamine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73620/1/j.1460-9568.1992.tb00183.x.pd

Ionic effects on the membrane potential of hyperpolarizing photoreceptor in scallop retina

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109976/1/tjp19782751345.pd

CB1 Receptor Antagonism Blocks Stress-Potentiated Reinstatement of Cocaine Seeking in Rats

Rationale Under some conditions, stress, rather than directly triggering cocaine seeking, potentiates reinstatement to other stimuli, including a subthreshold cocaine dose. The mechanisms responsible for stress-potentiated reinstatement are not well defined. Endocannabinoid signaling is increased by stress and regulates synaptic transmission in brain regions implicated in motivated behavior. Objectives The objective of this study was to test the hypothesis that cannabinoid type 1 receptor (CB1R) signaling is required for stress-potentiated reinstatement of cocaine seeking in rats. Methods Following i.v. cocaine self-administration (2 h access/day) and extinction in male rats, footshock stress alone does not reinstate cocaine seeking but reinstatement is observed when footshock is followed by an injection of an otherwise subthreshold dose of cocaine (2.5 mg/kg, i.p.). CB1R involvement was tested by systemic administration of the CB1R antagonist AM251 (0, 1, or 3 mg/kg, i.p.) prior to testing for stress-potentiated reinstatement. Results Stress-potentiated reinstatement was blocked by both 1 and 3 mg/kg AM251. By contrast, AM251 only attenuated food-reinforced lever pressing at the higher dose (i.e., 3 mg/kg) and did not affect locomotor activity at either dose tested. Neither high-dose cocaine-primed reinstatement (10 mg/kg, i.p.) nor footshock stress-triggered reinstatement following long-access cocaine self-administration (6 h access/day) was affected by AM251 pretreatment. Footshock stress increased concentrations of both endocannabinoids, N-arachidonylethanolamine and 2-arachidonoylglycerol, in regions of the prefrontal cortex. Conclusions These findings demonstrate that footshock stress increases prefrontal cortical endocannabinoids and stress-potentiated reinstatement is CB1R-dependent, suggesting that CB1R is a potential therapeutic target for relapse prevention, particularly in individuals whose cocaine use is stress-related

An intensity-dependent biphasic neuron in mudpuppy retina

Intracellular recordings in dark-adapted mudpuppy retinas have revealed a type of infrequently encountered cell with unusual response properties. These cells may be a subclass of horizontal cell since they are encountered at the same depth as horizontal cells and have large receptive fields and response amplitudes. However, they differ from typical horizontal cells in that they are depolarized by low intensity illumination and hyperpolarized by higher intensity illumination at all wavelengths. Both types of responses appear to be driven mainly by 572 nm cones. Both the depolarizing and hyperpolarizing responses were unaffected by APB, indicating that they are not mediated by on-center bipolar cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29940/1/0000297.pd

The effect of cholinergic agonists and antagonists on ganglion cells in the mudpuppy retina

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26465/1/0000553.pd

Excitatory amino acids have different effects on horizontal cells in eyecup and isolated retina

Horizontal cells in the mudpuppy eyecup responded to continuous superfusion with -gluamate, -aspartate, kainate and quisqualate with a transient depolarization and reduction of the light evoked responses. However, in isolated retina preparations, in which these substances were applied to the photoreceptor side of the retina, the effects were sustained as long as the agonists were present. These results suggest that the transient action of these agonists in eyecup preparations was due to the rapid development of an intraretinal diffusion barrier, and are consistent with the hypothesis that photoreceptors release an excitatory amino acid transmitter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26915/1/0000481.pd

Light-evoked sustained inhibition in mudpuppy retinal ganglion cells

Intracellular recordings were made from off-center ganglion cells in the retina of the mudpuppy. Necturus maculosus. Current-voltage measurements revealed that the sustained light-evoked hyperpolarization of these cells is due to a sustained inhibitory synaptic input with a reversal potential more negative than the resting potential.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24107/1/0000364.pd

Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake2-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake