Dual mechanisms of opiate dependence in the locus coeruleus.
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Animals↗
Biomedical subjects
M Alreja
Publications and source records attributed to M Alreja.
Activation of locus coeruleus (LC) neurones by cholera toxin: mediation by cAMP-dependent protein kinase.
There is evidence that the tonic pacemaker activity of the noradrenergic pacemaker neurones of the locus coeruleus (LC) depends on endogenous cAMP acting via protein kinase A and its phosphorylation pathway. In this study, we tested the effect of cholera toxin, which produces persistent activation of Gs, on LC firing rates. Bath applied cholera toxin (holotoxin) increased LC firing rates after a lag of 50-110 min. Intracellularly applied A-subunit (active-subunit) but not the B-subunit (binding-subunit) of cholera toxin via low resistance patch electrodes mimicked the excitatory actions of bath-applied holotoxin but without its lag period. The effects of both bath-applied and intracellularly applied cholera toxin A-subunit were blocked by intracellular applications of a specific cAMP-dependent protein kinase inhibitor (PKI5-24). We conclude that persistent activation of Gs by cholera toxin (A-subunit) increases LC firing rates via the cAMP-dependent protein phosphorylation pathway.
Action Potentials↗
Pacemaker activity of locus coeruleus neurons: whole-cell recordings in brain slices show dependence on cAMP and protein kinase A.
Noradrenergic neurons of the rat locus coeruleus (LC) are endogenous pacemakers that exhibit slow, tonic firing even in the complete absence of synaptic inputs. In the present study a time-dependent decline in LC spontaneous firing activity was found on intracellular dialysis during whole-cell recording with low-resistance patch electrodes; this decline was accentuated by a specific inhibitor of cAMP-dependent protein kinase (PKI5-24). Conversely, the inclusion of cAMP, 8-Br-cAMP, or the catalytic subunit of cAMP-dependent protein kinase (PKAcat) in the patch pipettes dose-dependently increased firing rate; intracellular PKI5-24 blocked both 8-Br-cAMP and PKAcat-induced firing in LC neurons. These results indicate that endogenous cAMP, via a phosphorylation-dependent route, drives tonic pacemaker activity in LC neurons.
Animals↗
Psychophysical studies of the itch sensation and itchy skin ("alloknesis") produced by intracutaneous injection of histamine.
Psychophysical measurements of itch and itchy skin ("alloknesis"--itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections of histamine or papain into the volar forearm. Histamine and papain were given in doses of 0.1, 1, or 10 micrograms in 10 microliters of saline. The effects of the depth of injection and of skin temperature on the latency, magnitude, and duration of itch were examined. Also, dose-response functions were obtained for the area of alloknesis produced by intracutaneous injections of histamine. Finally, the neural mechanisms underlying the spread of alloknesis were investigated via local anesthesia of the skin. Intracutaneous and subcutaneous injections of histamine, but not papain, produced a sensation of itch without pain. The latency of itch was shorter after an intracutanous than after a subcutaneous injection of histamine. The mean latencies of itch produced by a 1-microgram dose were 9.5 and 23.0 sec for intracutaneous and subcutaneous injections, respectively. No differences were observed in the magnitude or duration of itch. Similarly, the latency of itch was increased when the skin temperature at injection site was lowered to 15 degrees C, whereas the magnitude and duration of itch were unaffected. Intracutaneous and subcutaneous injections of histamine produced similar areas of alloknesis. However, the magnitude and duration of alloknesis were dependent on dose. The mean maximum areas of alloknesis produced by intracutaneous injections of 0.1, 1, and 10 micrograms of histamine were 28.3, 47.2, and 43.8 cm2, respectively. Alloknesis was present at 2 min after injection, increased to a maximum area without 10 min, and then gradually decreased during the next 25-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Behavioral scoring using programmable calculators: a technique usable in the field.
A simple method of recording the time spent in various behavioral categories during behavioral scoring is described. Use is made of a programmable calculator which is made to function as a multiple timer, keeping track of each of the categories. Any number of mutually exclusive categories can be scored using a single key press, by assigning a pre-set code to each. A print-out of the analysed frequency or duration data can be obtained either concurrently or at any time after the experiment, as required. The least count of the technique is about 1-2 seconds and this precludes its use for extremely rapidly changing behaviors. Apart from this, it is convenient, time-saving and especially suitable for field use.
Computers↗