Sexual
behavior in male rats after radiofrequency or
dopamine-depleting lesions in nucleus
accumbens
Liu YC, Sachs BD, Salamone JD.
Department of Psychology,
and Biobehavioral Sciences, University of
Connecticut, USA.
Abstract
Considerable neurochemical evidence links
dopamine (DA) in nucleus accumbens (NAcc) to
male sexual behavior. The present experiments
were conducted to extend this information to the
male's sexual response to remote stimuli from
estrous female (noncontact erection; NCE). Male
rats were tested for copulation and NCE after
either 6-hydroxydopamine (6-OHDA) or
radiofrequency (RF) lesions in NAcc). Males with
an average 78% depletion of DA in NAcc had a
lower incidence of NCE, longer latency to
display NCE, and fewer erections. DA-depleted
males also had less locomotor activity after
injections of d-amphetamine, and reductions in
apomorphine-induced yawning, but a normal
incidence of penile erection. Males with RF
lesions of the NAcc had longer NCE latencies.
All males copulated to ejaculation after either
6-OHDA or RF lesions with little or no deficit,
although the 6-OHDA-treated males had longer
intromission latencies. The NCE deficit supports
the hypothesized role of NAcc DA in arousal
processes in responding to remote cues from
estrous females. The minimal effect of lesions
on copulation suggests that the presence of
additional proximal stimulation during
copulation may overcome the deficits induced by
DA depletions or lesions in NAcc.
NEUROCHEMICAL and lesion studies have
yielded conflicting evidence about the role of
dopamine (DA) in nucleus accumbens (NAcc) in
male sexual behavior. Microdialysis studies have
demonstrated that extracellular DA is increased
when male rats are exposed to inaccessible
estrous females (6,29), and remains elevated
during copulatory behavior and until ejaculation
(6,32,44). DA-related voltammetric signals
increase during sexual behavior (19,21,31) and
with the presentation of novel odors associated
with estrous females (45). Yet despite the
evidence indicating that accumbens DA release is
associated with aspects of male sexual behavior,
the precise role of DA in sexual behavior
remains unclear. Recent voltammetric evidence
indicates that DA-related signals increase in
response to chasing, mounting, and intromission
(22). Yet these markers of extracellular DA
actually decrease with ejaculation (22),
suggesting that accumbens DA release does not
mediate the hedonic aspects of ejaculation. In
addi-
tion, evidence from studies employing cell
body or DAdepleting lesions of the NAcc
indicates that damage to this brain area has
little or no effect upon male sexual behavior.
Depletions of accumbens DA by local injections
of the neurotoxic agent, 6-hydroxydopamine
(6-OHDA), delayed the initiation of copulation
in male rats (9,33), but did not change the
number of mounts or intromissions, nor did they
alter the intromission ratio, a common index of
erectile function in copula (9). Neither
electrolytic lesions (2) nor blockade of DA
receptors in accumbens by local injections of
haloperidol (30) caused more than minor
impairment of copulatory behavior. Injections of
apomorphine into the ventral tegmental area to
decrease DA neuron activity resulted in motor
slowing, but did not alter the selection of
estrous females by male rats in an X-maze
procedure (15). Thus, despite the neurochemical
changes seen in NAcc that are associated with
male sexual behavior, pharmacological or
neurotoxic disruption of accumbens DA, as well
as lesions of the intrinsic cell bodies of this
structure, leave fundamental aspects of sexual
behavior and motivation intact.
Of course, it remains possible that aspects
of sexual behavior that are not usually assessed
in standard tests of copulation would be
affected by accumbens DA depletions. For
example, responding on a higher order schedule
for sexual reinforcement was affected by
accumbens DA depletions (9). This is consistent
with other data indicating that accumbens DA is
involved in responsiveness to conditioned
stimuli or remote cues (3,9,33,39,40,42).
Recently, procedures have been developed for the
assessment of noncontact erections (NCEs) (38).
NCEs, which occur in response to remote cues
from estrous females, are thought to be related
to the autonomic arousal that is characteristic
of sexual responsiveness (34,35). NCEs are
analogous to human psychogenic erections,
usually defined as erections initiated by brain
centers in response to visual, auditory,
chemosensory, or imaginative stimuli (23,34,35).
Previous research has indicated that brain
structures involved in NCEs can be dissociated
from those that mediate copulatory behavior. In
rats, excitotoxic or radiofrequency lesions of
the medial preoptic area substantially impaired
copulatory behavior, but did not alter NCEs
(18). Conversely, radiofrequency lesions of the
medial amygdala (17) or bed nucleus of the stria
terminalis (18) severely impaired NCEs, but they
caused only moderate impairment of copulation.
Thus, it is possible that manipulations of the
NAcc could alter NCEs, despite the fact that
these same conditions would have little effect
upon copulatory behavior.
The present experiments were conducted to
explore the role of the NAcc in mediating NCE in
male rats. We examined the effects of 6-OHDA
depletion of DA in the NAcc on NCE and
copulatory behavior. In a separate experiment,
we also studied the behavioral effects of
radiofrequency lesions in the NAcc. Males with
6-OHDA lesions were also tested for
apomorphine-induced penile erection and
yawning, and for d-amphetamine-induced
locomotor activity.
DISCUSSION
In these experiments, cell body or
DA-depleting lesions of the NAcc significantly
impaired NCE behavior. After accumbens DA
depletions, the NAccd males had significantly
longer latencies to the first erection in both
NCE tests compared to vehicle-control males
(Fig. 2). The incidence of NAccd males
displaying NCE (Fig. 1) and the number of
erections (Table 2) tended to be smaller than
vehicle controls in both tests, but were
significant only in test 2. Males with RF
lesions of NAcc had the same trend as
6-OHDA-treated males for the incidence of
displaying NCE (Fig. 1), NCE latencies (Fig. 4),
and the number of erections (Table 2) in both
tests, but group differences were reliable only
for NCE latency in test 2. The significantly
longer latency to first NCE (three of four tests
across experiments) and the modest reduction in
number of NCEs (one of four tests across
experiments) in males with NAcc lesions or DA
depletions suggests that NAcc is a part of the
neural circuitry that regulates the display of
NCEs. These results support the view that the
NAcc participates in sexual arousal processes
(9,14,30,44).
Previous work has shown that olfactory cues
are essential for evoking NCE (8,37), and
lesions of medial amygdala eliminate this sexual
response (17). The NAcc receives olfactory
input, particularly through projections from the
medial amygdala to the shell part of the
accumbens (4,12,46). It has been suggested that
the NAcc is a "limbic-motor interface" for
translating sensory and emotional processes into
motor output (25), and that dopaminergic
modulation of the activity of neurons in
accumbens could serve a "gating" function to
influence output (40,41). In addition, DA in
NAcc has been implicated in the modulation of
behavioral responsiveness to conditioned or
remote incentive stimuli (9,33,39,40,42). Thus,
in view of the fact that NCE tests measure
behavioral responses to remote cues from
inaccessible estrous females (38), the results
obtained from the present studies are consistent
with previous hypotheses of NAcc function.
However, the present results are unique in that
the response being disrupted by interference
with NAcc is not a skeletal motor response such
as locomotion or lever pressing, but apparently
includes an autonomically mediated response,
i.e., penile erection. This inference should be
tested by direct measures of erection, rather
than the indirect ones used in these studies,
because of the possibility that disruption of
NAcc function interfered only with the motor
component of NCE.
In the 6-OHDA experiment, DA in NAcc was
depleted by 78% in 6-OHDA-treated males relative
to vehicle-treated rats. These depletions were
substantial enough to affect NCE and reduce
amphetamine-induced locomotion, although 6-OHDA
treatment had little effect on several aspects
of copulatory be-
havior. Despite the fact that the
intromission latencies of NAccd males were
longer than vehicle-injected males, experimental
and control males were similar on all other
measures of copulatory behavior in the 6-OHDA
experiment, as well as in the RF lesion study.
In particular, it should be emphasized that the
lesion and control groups in both experiments
had similar intromission ratios, suggesting that
NAcc lesions did not impair erectile function
during copulation. The relative preservation of
copulatory function after NAcc lesions or DA
depletions is generally consistent with previous
studies, reviewed above, using various
techniques to impair NAcc function (2,30,33). In
addition, the lack of effect on nose pokes after
cell body or DA-depleting lesions suggests that
any deficit in NCE was not due to reduced
attention to the female. Thus, despite the fact
that cell body or DA-depleting lesions of NAcc
disrupted NCE, several other aspects of sexual
behavior were left intact after these
manipulations. Clearly, it would be an
oversimplification to state that accumbens DA
depletions or lesions impaired "motivation,"
"reward," "preparatory behavior," or even
"erections," without further qualification; the
deficits in erectile function produced by
lesions or DA depletions of accumbens were
highly context specific.
There are many reports that extracellular DA
levels in the NAcc increase during copulation
until ejaculation (6,10,21,29, 32,44). However,
depleting accumbens DA had relatively little
effect on copulatory behavior [(33) and
present article]. Previous reports have
indicated that the response-suppressing effects
of interference with DA function can be
overridden by increasing the sensory input (40).
For example, changing environmental stimulation
reversed the decline in locomotion in-
duced by treating rats with haloperidol
(20). In the present experiments, the proximal
stimuli from the female during the copulation
tests may have overcome the lesion-induced
deficit that was manifest in the NCE tests, in
which only remote cues from the female were
available to the male.
Systemic administration of low doses of the
DA agonist, apomorphine, can induce penile
erection and yawning in rats (11,24,26).
This effect can be blocked by pretreatment with
the DA antagonist, haloperidol (11,43). Several
previous studies indicated that the behavioral
effects of systemic apomorphine treatment are
mediated by multiple sites within the brain. For
example, electrolytic lesion of the
paraventricular hypothalamus (PVH) abolished
apomorphine-induced erections and yawning
(1). Depletions of striatal DA by injections of
6-OHDA into caudate putamen also abolished
apomorphine-induced erections and yawning
(7). Microinjection of apomorphine (1 g) into
PVH induced both penile erection and
yawning, but similar injections into NAcc
were ineffective (24). Our data suggest that
NAcc DA does play a role in apomorphine-induced
yawning, but little or no role in
apomorphine-induced penile erection. It is
possible that accumbens DA depletions reduced
the effect of apomorphine on yawning
because the DA depletions resulted in DA
receptor supersensitivity, which eliminated the
yawning effect of apomorphine that
normally occurs at a relatively low dose. In
addition, the lack of effect of DA depletions on
apomorphine-induced penile erections suggests
that erections induced by remote cues from
females and those induced by apomorphine are
regulated by different brain mechanisms.
In summary, male rats with depletions of
accumbens DA had deficits in NCE, which supports
the hypothesized role of NAcc DA in sexual
arousal processes involved in responding to
remote cues from estrous females. After
incurring cell body or DA-depleting lesions of
NAcc, these males had little or no deficit in
nose pokes or copulatory behavior. We therefore
infer that the deficit in NCE was not due to a
reduction of attention to the females or to a
severe deficit in sexual motivation.
