Biomedical subjects

J Malette

Publications and source records attributed to J Malette.

4 recordsLinked to original sources

PubMed1995

Interhemispheric links in brain stimulation reward.

The MFB substrate of self-stimulation (SS) has generally been viewed as a unilateral system. We re-examined this belief with pairs of moveable SS electrodes placed bilaterally in the MFB. Rats barpressed for trains of single or twin cathodal pulses of fixed intensity and width and of variable frequency. The first (C) and second (T) pulse of each pair was delivered through the left and right electrode or inversely. C-T intervals ranging from 0.2 to 5.0 ms were tested. The frequency of C pulses required for criterial bar-pressing was used to plot the stimulation efficacy (SE), as a function of the C-T interval and pulse presentation order. The electrodes were subsequently moved and the same procedure repeated for more ventral sites. With some pairs of contralateral hypothalamic (H) sites, the SE was independent of the C-T interval. However, with other pairs of contralateral H sites, the SE increased with C-T interval in a manner resembling a collision effect, with the important exception that no conduction time (CT) was apparent in the data. The absence of CT excludes the presence of a genuine collision effect. When one pulse was sent to the H and another to the contralateral ventral tegmentum (VT), the H-VT curve rose always earlier than the VT-H curve, thus resembling a transynaptic collision effect. However, the C-T interval at which the VT-H curve began rising (always 1.0 ms or less) fails to support the contention that the electrodes activated fibers separated by a synapse. Finally, a typical collision effect was noted with ipsilateral H-VT electrode placements, confirming the presence of direct linkage between ipsilateral MFB sites. Computer-generated data based on two parsimonious assumptions were found to match the empirical results. These assumptions were that each electrode activated a different branch of the same reward neuron and that conduction failure occurred at the branchpoint. The model, which posits that a large number of MFB reward neurons send branches to the other hemisphere, is testable and makes clear-cut predictions about the effects of lesions. In a preliminary test, we recorded the H and contralateral VT threshold frequencies before and after lesioning the H. The H threshold increased more when using small pulse current and remained constant throughout the 4-week testing period. The VT threshold was elevated more for intermediate pulse current and kept increasing with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

The notion of response invariance in trade-off studies of self-stimulation.

Trade-off profiles, displaying the co-variations of 2 electrical parameters required to maintain a constant magnitude of brain stimulation reward (BSR), have been used extensively in order to characterize the self-stimulation (SS) neurons. It has often been assumed that constancy in the magnitude of BSR can be achieved more accurately by holding SS at a constant proportion of the maximum rate, rather than at a constant rate. The validity of this assumption was tested in 2 experiments using rats. In Exp. 1, we first computed the function that relates SS barpressing rate to pulse frequency (RF function) for two different pulse intensities, separately. The peak SS rate was found to be lower in the low current than in the high current RF function. The rats were then placed in a 2-lever box and were allowed to select either a fixed frequency of the high current pulses or a variable frequency of the low current pulses. In Exp. 2, the RF function was first computed for 2 different lever weights, separately. The peak SS rate was found to be lower in the heavy-lever RF function than in the light-weight lever RF function. The rats were then allowed to select either a fixed pulse frequency delivered by the heavy lever or a variable pulse frequency delivered by the light-weight lever. Isopreference was noted in both experiments, for pulse frequencies which, in the single-lever box, elicited the same proportion of the maximum SS rate, not the same SS rate. The data thus validate the idea that a constant magnitude of BSR is translated into a constant proportion of the maximum SS rate, not a constant SS rate.

Animals↗

PubMed1987

Summation and saturation properties in the rewarding effect of brain stimulation.

We used a two-lever self-stimulation chamber and rats with central grey and hypothalamic electrodes to obtain a choice-frequency (C/F) function, which plots the relative choice of an electrical stimulus of fixed pulse frequency (the standard stimulus) as a function of the frequency of a second competing stimulus (the alternative stimulus). A family of C/F functions was obtained using increasing frequencies for the standard. A choice index, varying from -1.0 (exclusive choice of the fixed stimulus) to 1.0 (exclusive choice of the alternative stimulus) was computed by using the barpressing rates on the two levers. Reward saturation was assumed to occur when the C/F function obtained with the largest standard reached an asymptote below the value of 1.0. For the hypothalamic subjects, the pulse frequency at the point of reward saturation was twice as high as the frequency required for the maximum rate of self-stimulation in the usual single-lever chamber. Decreasing the pulse intensity always increased the saturation frequency, indicating that the saturation was not due to a frequency blocking effect in the directly activated neurons. Reward saturation occurred with a considerably higher frequency in the central grey than in the hypothalamus. Thus, the asymptotic rate of self-stimulation in the usual single-lever chamber is not conditioned by the processes that summate the central grey and hypothalamic rewarding effects. From the central grey data we obtained the relation between the slope and the position of the C/F function on the frequency axis. We used the slope/frequency profile to delimit the most probable profile of summation rate in the rewarding process. We found that the slope/frequency function has an early plateau followed by a rapidly decelerating phase. We proposed that these two distinct phases reflect an early accelerating rate of summation, followed by a decelerating rate of summation. In other words, reward summation would be predicted by a sigmoid growth model.

Animals↗

PubMed1986

The effects of pimozide on the reinforcing efficacy of central grey stimulation in the rat.

The present report describes the effects of the neuroleptic pimozide on the reinforcing efficacy of central grey stimulation. Six adult rats were implanted with a monopolar moveable stimulating electrode in the pontine central grey. Each bar-press in an operant chamber delivered a 0.3-s train of cathodal rectangular pulses of constant duration (0.1 ms) and intensity (from 180 to 440 microA depending on the subject) and of variable frequency. The function relating the rate of bar-pressing to the logarithm of the number of pulses per train (rate-frequency function) was recorded following administration of vehicle and increasing doses of pimozide (from 0.15 to 0.5 mg/kg). Pimozide produced a dose-dependent parallel shift of the rising segment of the rate-frequency function towards higher pulse numbers in 4 subjects, indicating that the drug reduced the reinforcing efficacy of the stimulation. In two subjects, the shift was accompanied by a decrease in slope of the rising segment. Depending on the subject, the greatest shift observed varied from 0.087 to 0.489 log units. Further attempt to increase the magnitude of shift with higher doses resulted in complete abolition of self-stimulation. The fact that pimozide reduced the value of reward in an area containing only marginal amounts of dopaminergic cells adds support to the hypothesis that dopamine modulates reward indirectly. The fact that the shift could not be increased with higher doses was interpreted as an indication that dopaminergic neurons are involved in a gate-like synaptic arrangement in which a limited decrease in dopaminergic activity is sufficient to obliterate the transmission in the reward pathway or the conversion of the signal into a reinforcing effect.

Animals↗