Excitotoxic lesions of the tegmental pedunculopontine nucleus impair copulation in naive male rats and block the rewarding effects of copulation in experienced male rats

Abstract

The tegmental pedunculopontine nucleus (TPP) of the brainstem mediates food reward in food-sated animals and opiate reward in drug-naive animals. In the present study, we examine the effect of excitotoxic lesions of the TPP on sexual behaviour in naive and experienced male rats. Male, Long-Evans rats received either 0.25 micro L injections of NMDA (4.2 micro g/side) or vehicle (shams) into the TPP. In sexually naive males, complete bilateral TPP lesions decreased all measure of copulation (i.e. mounts, intromissions and ejaculations), prevented acquisition of conditioned sexual excitement, decreased approach preference for a receptive female over a non-receptive one, and decreased non-contact erections; unilateral or bilateral posterior-sparing TPP lesions did not affect any of these measures. Conversely, in sexually experienced males, lesions not only failed to disrupt copulation, but also increased conditioned sexual excitement, decreased post-ejaculatory interval and blocked the effect of prolonged copulation on conditioned sexual excitement. Following differential pairing of distinctive environments with and without copulation, sham males with sexual experience displayed a significant preference for the environment paired with copulation, whereas the lesion males with sexual experience displayed a significant aversion for the environment paired with copulation. These findings indicate that the TPP is critical for the acquisition of copulation in naive males and mediates the rewarding consequences of copulation in experienced males. Together these findings demonstrate that the TPP mediates sexual reward, but that sexual experience is not sufficient to produce a deprivation state.

Pedunculopontine Tegmental Nucleus Controls Conditioned Responses of Midbrain Dopamine Neurons in Behaving Rats

“…Previous studies have shown that integrity of PPTg is necessary for arousal, attention, motivation and learning, and, particularly interestingly here, stimulus-reward associations (Steckler et al, 1994b). Studies using a variety of conditioning tasks have suggested a role for PPTg in assigning task-specific salience value to cue signals (Inglis et al, 1994(Inglis et al, , 2000Florio et al, 1999;Kippin and van der Kooy, 2003). Consistent with this idea, some PPTg cells in cat were found to respond to conditioned stimuli in a context-dependent way, failing to respond to the same cue when another signal indicated a different task requirement (Dormont et al, 1998).…”

D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of G q /11 in the striatum

“…GDP (final concentration, 1 M) was added to 100-g membranes from HEK cells or striata of wild-type, D1 mutant mice (22), or D2 mutant mice (23), and the assay mixture was incubated on ice for 10 min. The mixture was moved to 30°C and then incubated for 5 min before adding [ 35 S]GTP␥S (1,250 Ci/mmol) (PerkinElmer, Wellesley, MA) to a final concentration of 2.5 nM.…”

MK-801 infusions to the ventral tegmental area and ventromedial hypothalamus produce opposite effects on lordosis of hormone-primed rats

“…It is particularly important to ascertain the mechanisms underlying progestins actions for mediating reinforcing behaviors, given the potential role of progesterone in mediating response to drugs of abuse (Frye, submitted for publication). Furthermore, given that neuronal adaptations in the ventral tegmental area have been proposed to account for the progressive transition from non-dependence to drug dependence, model systems such as this (Kippin and van der Kooy, 2003) are particularly valuable as they are free from potential confounds of direct drug-related effects and can be used to examine neural substrates for particularly salient motivated behaviors (Berridge and Robinson, 1998;Koob and Le Moal, 2001;Spanagel et al, 1993).…”