Sexual activity increases dopamine transmission in the nucleus accumbens and striatum of female rats.

In vivo microdialysis was used to monitor extracellular concentrations of dopamine (DA), and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and dorsal striatum of sexually active female rats during tests of locomotor activity, exposure to a novel chamber, exposure to sex odors, the presentation of a sexually active male rat, and copulation. DA increased slightly but significantly in the nucleus accumbens when a sexually active male was placed behind a wire-mesh screen, and further during copulation. DA also increased significantly in the dorsal striatum during copulation; however, the magnitude of this effect was significantly lower than that observed in the nucleus accumbens. The metabolites DOPAC and HVA generally followed DA with a delay, and increased significantly during copulation in both regions. In contrast, forced locomotion on a rotating drum, exposure to a novel testing chamber, and exposure to sex odors did not increase DA significantly in either region, although forced locomotion increased DOPAC significantly in both regions, and HVA significantly in the nucleus accumbens. The magnitude of DA release in the nucleus accumbens was significantly greater during copulation than running, whereas no significant difference was detected for striatal DA release between these two behavioral conditions. These results indicate that novelty or locomotor activity alone do not account for the increase in DA observed in the nucleus accumbens of female rats during copulation, and suggest that DA transmission in the nucleus accumbens is associated with anticipatory and consummatory aspects of sexual activity, as it is in male rats. In the dorsal striatum, however, DA release during copulation may reflect an increase in locomotor activity associated with active pacing of the male.

Dopamine transmission increases in the nucleus accumbens of male rats during their first exposure to sexually receptive female rats.

In vivo microdialysis was used to monitor extracellular concentrations of dopamine (DA), and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the nucleus accumbens of sexually naive male rats during their first exposure to sexually receptive or nonreceptive females. DA, DOPAC, and HVA increased progressively and significantly in males that copulated to ejaculation with receptive females. In contrast, DA, DOPAC, and HVA did not increase significantly in males exposed to non-receptive females, despite several attempts by these males to mount the non-receptive females. These results indicate that DA is released unconditionally in the nucleus accumbens of male rats by exposure to sexually receptive female rats, and that copulation with intromission, but not mounting alone, leads to further increases in DA release.

Effects of chronic bupropion on interstitial concentrations of dopamine in rat nucleus accumbens and striatum.

Bupropion is a novel atypical antidepressant that inhibits dopamine (DA) uptake. The present experiments investigated the effects of acute (10 mg/kg, twice daily for 2 days) and chronic (10 mg/kg, twice daily for 21 days) bupropion treatment on interstitial DA concentrations using simultaneous in vivo microdialysis in the nucleus accumbens (NAC) and striatum of awake freely moving rats. Compared to animals that had not previously been exposed to the drug, bupropion (25 mg/kg, IP) induced increases in extracellular DA were significantly enhanced in the NAC of the chronic but not the acute bupropion group. This effect was regionally selective, as it was not observed in the striatum. In accordance with previous reports, concurrent behavioral measurements indicated that the locomotor stimulant effects of bupropion were also enhanced in the chronic group. These results demonstrate that bupropion-induced behavioral sensitization is accompanied by a selective potentiation of the effects of this compound on interstitial DA concentrations in the NAC.

Sexual behavior increases dopamine transmission in the nucleus accumbens and striatum of male rats: comparison with novelty and locomotion.

Extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were examined concurrently, using in vivo microdialysis, in the nucleus accumbens and dorsal striatum of sexually active male rats during tests of locomotor activity, exposure to a novel chamber, exposure to sex odors, the presentation of a sexually receptive female, and copulation. DA increased significantly in the nucleus accumbens when the males were presented with a sexually receptive female behind a screen and increased further during copulation. Although DA also increased significantly in the dorsal striatum during copulation, the magnitude of the effect was significantly lower than that observed in the nucleus accumbens. In contrast, forced locomotion on a rotating drum, exposure to a novel chamber, and exposure to sex odors did not increase DA significantly in either region, although both DOPAC and HVA increased significantly in both regions during the locomotion test. These results indicate that novelty or locomotor activity alone cannot account for the increased extracellular DA concentrations observed in the nucleus accumbens of male rats during the presentation of a sexually receptive female behind a screen, nor can they account for the increased DA concentrations observed in both the nucleus accumbens and dorsal striatum of male rats during copulation. The preferential increase in DA transmission in the nucleus accumbens, compared with that in the striatum, suggests that anticipatory and consummatory aspects of sexual activity may belong to a class of naturally occurring events with reward values that are mediated by DA release in the nucleus accumbens.

Chronic desipramine enhances amphetamine-induced increases in interstitial concentrations of dopamine in the nucleus accumbens.

There is accumulating evidence that some antidepressant treatments can increase the functional output of the meso-accumbens dopaminergic system. For example, chronic administration of tricyclic antidepressant drugs such as imipramine and desipramine (DMI) enhances the locomotor stimulant effects of d-amphetamine. Subsensitivity of inhibitory dopamine (DA) autoreceptors and supersensitivity of postsynaptic DA receptor mechanisms are among the mechanisms that have been suggested to underlie these observations. The present experiments investigated the effects of acute and chronic DMI treatment on interstitial DA concentrations in the nucleus accumbens and striatum using in vivo microdialysis in awake freely moving rats (48 h following implantation of a microdialysis probe). Neither acute (5 mg/kg b.i.d. for 2 days followed by 72 h withdrawal) nor chronic (5 mg/kg b.i.d. for 21 days followed by 72 h withdrawal) DMI influenced the ability of apomorphine (25 micrograms/kg s.c.) to decrease extracellular concentrations of DA or its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens. In contrast, d-amphetamine (1.5 mg/kg s.c.)-induced increases in extracellular DA were significantly enhanced in the nucleus accumbens of the chronic but not the acute DMI group. This effect was at least partially regionally selective, as significant effects were not observed in the striatum. In accordance with previous reports, the locomotor stimulant effects of d-amphetamine were also enhanced in the chronic DMI groups. DMI itself failed to alter the interstitial concentrations of DA and its metabolites in the nucleus accumbens of the control and chronic DMI groups. These results provide in vivo neurochemical confirmation that chronically administered DMI does not produce DA autoreceptor subsensitivity. They also demonstrate that chronic DMI-induced increases in the locomotor stimulant effects of d-amphetamine are accompanied by a selective potentiation of the effects of this stimulant on interstitial DA concentrations in the nucleus accumbens.

Sexual behavior enhances central dopamine transmission in the male rat.

Central dopamine transmission was examined in the nucleus accumbens and striatum of sexually experienced male rats during mating behaviour using in vivo brain microdialysis. Dopamine release increased significantly in the nucleus accumbens when males were placed in a novel mating chamber and when a receptive female was introduced behind a screen partitioning this chamber. Subsequently, during copulation dopamine transmission increased sharply, this being followed by a gradual decrease after the female was removed. In contrast, striatal dopamine transmission increased significantly only during copulation. These data provide a neurochemical basis for the well-known interactions between dopaminergic drugs and male sexual behaviour and demonstrate the feasibility of using brain microdialysis to elucidate the neurochemical correlates of motivated behaviour.

Effects of transient forebrain ischemia and pargyline on extracellular concentrations of dopamine, serotonin, and their metabolites in the rat striatum as determined by in vivo microdialysis.

Striatal microdialysis was performed in rats subjected to 20 min of transient forebrain ischemia produced by occlusion of the carotid arteries during hemorrhagic hypotension. Extracellular changes of dopamine, serotonin, and their metabolites were monitored before, during, and after the ischemic insult at 10-min intervals by on-line HPLC analysis. During ischemia, extracellular dopamine increased dramatically (156 times baseline), as did 3-methoxytyramine (3-MT), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (15-25% of baseline). Upon reperfusion, dopamine was cleared from the extracellular fluid within 40 min and reached a stable level (70% of baseline). DOPAC and HVA increased (250-330%) transiently and reached their maximum 1 h following reperfusion, whereas 3-MT decreased to undetectable levels within 20 min. Although baseline levels of serotonin were not detectable, serotonin and 5-hydroxyindoleacetic acid showed a qualitatively similar temporal pattern to dopamine and its acid metabolites. Killing rats by cervical dislocation produced changes in extracellular dopamine, serotonin, and their metabolites that were almost identical to those seen during ischemia. Pargyline pretreatment 2 h before ischemia had marginal effects on the postischemic clearing of dopamine. The pargyline pretreatment, however, did increase the survival rate of rats subjected to ischemia, and this protective effect might be due to the pargyline-induced blockade of the post-ischemic monoamine oxidase-mediated increase in dopamine metabolism and the concurrent production of the potentially neurotoxic molecule, hydrogen peroxide.

In vivo characterization of locally applied dopamine uptake inhibitors by striatal microdialysis.

In vivo brain microdialysis was used to characterize the effects of some dopamine uptake inhibitors on the extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striata of awake, freely moving rats. d-Amphetamine, GBR 12909, cocaine, nomifensine, methylphenidate, bupropion, and benztropine were administered directly to the striatum via the perfusion fluid in increasing concentrations (1-1,000 microM). All drugs increased extracellular DA in a dose-dependent manner; however, only d-amphetamine produced dose-dependent decreases in DOPAC and HVA concentrations. The shapes of the dose-response functions differed considerably between the drugs. At 100 and 1000 microM d-amphetamine had biphasic effects (an increase followed by a decrease) on dialysate DA concentrations. GBR 12909, methylphenidate, and benztropine also had biphasic effects when applied at the 1,000 microM concentration. In contrast, cocaine, nomifensine, and bupropion produced relatively monophasic increases in extracellular DA. Tetrodotoxin (TTX), which prevents action potentials by blocking voltage-dependent Na+ channels, did not prevent d-amphetamine induced increases in extracellular DA, but blocked completely the effects of cocaine, nomifensine, bupropion, and methylphenidate. While low doses (10 microM) of GBR 12909 and benztropine were highly sensitive to TTX, the toxin was only partially effective against higher doses of the compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis.

This study examined the acute effects of the novel antidepressant drug, bupropion, on extracellular concentrations of dopamine (DA), its metabolites, and the serotonin metabolite 5-HIAA in the striatum and nucleus accumbens using on-line microdialysis in freely moving rats. Bupropion HCl (10, 25, and 100 mg/kg intraperitoneally) increased extracellular striatal DA in a dose- and time-dependent manner; 1 mg/kg did not affect extracellular DA. The maximal response occurred within the first 20 minutes (+76%, +164%, and +443% for each dose, respectively) followed by a gradual decrease to a stable but elevated level for the next 2 hours. This neurochemical response was strongly associated with bupropion-induced stereotyped behavior during the first hour but not during the subsequent 2 hours. Bupropion decreased DOPAC concentrations, increased 5-HIAA, and had variable effects on homovanillic acid (HVA) (decreases with 10 mg/kg and increases with 25 and 100 mg/kg). The increase in extracellular DA after bupropion (25 mg/kg) was blocked by tetrodotoxin and was therefore action-potential-dependent. Bupropion produced similar neurochemical responses in the striatum and the nucleus accumbens. These results suggest that increases in DA transmission contribute to the behavioral effects of bupropion and are consistent with a role for DA in the antidepressant effects of this drug. The partial dissociation between DA release and stereotyped behavior suggests that the relationship between neurotransmitter release and behavior may be complex.

Irreversible antagonism of histamine H2 receptors in guinea-pig myocardium.

Dissociation constants and receptor reserves for histamine acting at H2 receptors in guinea-pig right atria and papillary muscles were measured using the irreversible H2 receptor antagonist L-643,441. Histamine alone was less potent in papillary muscles than in right atria, and maximum responses of papillary muscles to histamine were more susceptible to depression by L-643,441 than were maximum responses of right atria. However, dissociation constants (-log KA values) for histamine calculated using 3 different doses of L-643,441 were 0.5 log unit greater in papillary muscles than in right atria. A more marked difference was found in the estimates of receptor reserve for histamine, which appeared to be much greater in right atria than papillary muscles.