Brain Research 885 2000 154–165 www.elsevier.com locate bres
Temporary inactivation of the retrorubral fields decreases the rewarding effect of medial forebrain bundle stimulation
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Meg Waraczynski , Mark Perkins
Department of Psychology , University of Wisconsin-Whitewater, 800 W. Main St. Whitewater, WI 53190, USA
Accepted 22 August 2000
Abstract
Prior studies indicate that lesioning the retrorubral fields RRF decreases the rewarding effect of medial forebrain bundle MFB stimulation, although these studies did not make the RRF their primary target. This study directly investigates the role of the RRF in MFB
self-stimulation using transient lidocaine-induced inactivation of target tissue rather than permanent lesioning. In 18 rats with MFB stimulation electrodes, inactivation of the RRF via 0.5 and 1.0 ml of 4 lidocaine produced immediate, substantial upward shifts in the
frequency required to maintain half-maximal self-stimulation response rates whereas injecting comparable volumes of saline did not. Bilateral inactivation was particularly effective, especially at medium and high stimulation currents, although unilateral inactivation
ipsilateral to the stimulation site was also effective. Contralateral inactivation alone did not substantially change the stimulation’s reward value, although contralateral inactivation appeared to contribute to the effectiveness of bilateral inactivation. The frequency required to
maintain half-maximal responding returned to baseline levels by 15–20 min after lidocaine infusion. In seven rats whose infusion sites were not in the RRF, lidocaine inactivation did not consistently degrade the stimulation’s reward value. These results indicate that some
neural elements located in the RRF contribute to the rewarding effect of MFB stimulation. Possible roles for these elements in the anatomical substrate for MFB self-stimulation are discussed.
2000 Elsevier Science B.V. All rights reserved.
Theme : Neural basis of behavior
Topic : Motivation and emotion
Keywords : Brain stimulation; Rate–frequency curve shift; Lidocaine; Reward; Midbrain; Self-stimulation
1. Introduction median raphe lesion that strayed into the RRF was more
effective than accurately targeted lesions in reducing MFB Previous investigations of the anatomical substrate for
stimulation’s reward value [49]. Based on these findings, medial forebrain bundle MFB stimulation reward have
this report directly investigates the role of the RRF in MFB indicated that the midbrain retrorubral fields RRF may be
self-stimulation. an important component. Lepore and Franklin, in targeting
The RRF themselves support low rates of self-stimula- the nearby pedunculopontine tegmentum, noted that
tion [25]. The RRF are also of potential interest because NMDA excitotoxin lesions were most effective in impair-
the A8 dopamine cells are located there. MFB self-stimula- ing the acquisition of responding for MFB stimulation
tion is clearly linked to midbrain dopamine systems, when those lesions strayed rostrally to affect the RRF [29].
although dopaminergic neurons are not typically directly Similarly, we have recently reported that a mistargeted
activated by the stimulation [55]. Rewarding stimulation of both the MFB and midline mesencephalon increases
activity in at least some midbrain dopamine cells
Corresponding author. Tel.: 11-262-472-5415; fax: 11-262-472-
[7,10,24,32], although it should be noted that recently
1863.
several authors have questioned whether dopamine is
E-mail address : waraczymmail.uww.edu M. Waraczynski.
1
involved in the stimulation’s reward value per se or in
Current address: Department of Physiology, University of Wisconsin,
some other aspect of incentive motivation function e.g.
Medical Science Building, 1300 University Avenue, Madison, WI 53706, USA.
[21]; see [8] for a thorough review. Most attention has
0006-8993 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 9 0 8 - 5
M . Waraczynski, M. Perkins Brain Research 885 2000 154 –165
155
focused on the relationship between MFB self-stimulation cannulae were blocked with stylets made from 30 gauge
and the A9 and especially A10 cells of the substantia nigra tubing. The rats were housed individually with food and
and ventral tegmental area, respectively. Relatively little water continuously available in a day night reversed
attention has been paid to the A8 cells of the retrorubral colony. All testing was conducted during the dark phase of
fields, possible because these cells only comprise about the cycle.
10 of mammalian midbrain dopamine cells [33]. These cells have efferent control over both the A9 and A10
2.2. Procedures groups [6] and can be considered contiguous with the A9
and A10 groups [17]. A8 efferent projections often parallel 2.2.1. Rate–frequency testing
those of the A9 [19,31,46,51] and to some degree the A10 Rate–frequency testing was performed with the rat
e.g. [22] groups. A8 afference from the amygdala also placed in an operant chamber with a lever protruding from
parallels amygdaloid afference to the lateral A9 group one wall. The rat was connected to a Stimtek ST1200
[23,47]. Thus, the links between midbrain dopamine and stimulation generator San Diego Instruments via a flex-
self-stimulation also implicate the RRF as a target of ible cable and commutator Plastics One. All experimental
interest. events were controlled by Stimtek ST1000 CPU and
We have previously suggested that temporary inactiva- ST1100 I O boards in communication with a master PC.
tion of targets thought to be relevant to MFB stimulation After 3–5 days postsurgical recovery, the rats were
reward may be more effective, and more consistently trained to press a lever for a 0.5 s train of 0.1 ms cathodal
effective, than permanent lesions [1,48,49]. In part, this pulses delivered by a constant current generator. The rats
may be true because postlesion hyperexcitability in cells were trained using stimulation of either the LH or VTA
surrounding a lesion, and or synaptic plasticity in synapses site, whichever supported the more robust responding.
surviving the lesion, compensate for the loss of lesioned Once the lever press response was reliably established the
cells. Neither would be a factor if, instead of lesioning, rats would press without coaching for stimulation delivered
target tissue were rendered temporarily inactive via the on a VI 3-second schedule, the rat was tested at several
injection of an anesthetizing agent. In this report, we use pulse frequencies at 200, 400 and 800 mA at both sites.
lidocaine to temporarily inactivate cells in the RRF, both The site that yielded the lower and most consistent values
ipsi- and contralateral to MFB self-stimulation sites. of the frequency required to maintain half maximal per-
Changes in stimulation reward value are measured using formance at all three currents was chosen for all further
the rate–frequency curve shift method. If the RRF are testing.
important to the stimulation’s reward effect, then their Each point in a single rate–frequency curve was de-
inactivation should temporarily render MFB stimulation termined as follows: for 30 s, the rat was allowed to press
less rewarding. for a 0.5-s train of pulses of a given frequency, delivered
on a VI 3 s schedule. At the start of each 30-s trial, the rat received three non-contingent trains of the stimulation that
2. Methods would be available during that trial. Data from the first 10
