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Biomedical subjects

L Lumeng

Publications and source records attributed to L Lumeng.

At least 235 records · Page 13Linked to original sources

Effects of fluoxetine and desipramine on palatability-induced ethanol consumption in the alcohol-nonpreferring (NP) line of rats.

Three groups of NP rats (n = 5/group) received food, water and one of 3 Polycose solutions ad lib. One group received a solution containing 3% (w/v) Polycose, 0.125% (w/v) saccharin, 0.5% (w/v) NaCl (3% POL solution) to which ethanol was gradually added over three weeks until the concentration of 10% (v/v) ethanol (E) was reached (3% POL + E group). Alcohol ingestion by the 3% POL + E group reached an average of 9 g of ethanol/kg b. wt./day; the rats attained average blood alcohol concentrations of 61 +/- 8 mg%. One control group (3% POL) was given the same solution as above but without ethanol. The second control group (17% POL) had access to a 17.6% Polycose solution supplemented with 0.125% saccharin and 0.5% NaCl and was isocaloric to the 3% POL + E solution. Although the three groups differed significantly in the amounts of food and Polycose solutions consumed, their total caloric intakes were equivalent. The IP administration of the serotonin (5-HT) uptake inhibitor fluoxetine (5 and 10 mg/kg) significantly reduced drinking of the group receiving the 3% POL + E solution by 23% and 67%, respectively, but did not alter intakes of the Polycose solutions by the 3% or 17% POL control groups. The IP administration of the norepinephrine (NE) uptake inhibitor desipramine (5 and 10 mg/kg) significantly reduced intake of the Polycose solution by the 17% POL group by 52 and 83%, respectively, but only the 10 mg/kg dose attenuated drinking of the solutions by the 3% POL and 3% POL + E groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Persistence of tolerance in the P line of alcohol-preferring rats does not require performance while intoxicated.

Persistence of tolerance was measured seven days after a single ethanol injection (2.5 g/kg b. wt.) in the alcohol-preferring P line of rats with and without testing in a shock-motivated jump task during the initial ethanol exposure. P rats were trained to jump 50 cm to avoid shock and were assigned to one of three groups. On day 0, group E/J (n = 8) was injected with ethanol and tested on the jump task until recovery to criterion (37.5 cm), while group S/J (n = 21) was injected with saline and was tested yoked to an E/J rat. Rats in the E/NJ group (n = 19) received ethanol but were not tested on day 0. Seven days later, all rats received 2.5 g ethanol/kg and were tested to criterion. Recovery times on day 7 were significantly longer (p less than 0.05) for rats in the S/J group (169 +/- 7 min) than for the E/J (141 +/- 11 min) and E/NJ (145 +/- 6 min) rats. Blood ethanol concentrations at recovery for the E/NJ group were higher than the S/J group on day 7 and higher than the E/J group on day 0 (p less than 0.05). The results indicate that the persistence of tolerance manifested by the P rats is an inherited behavioral trait that requires only ethanol exposure.

Alcohol Drinking↗

Alcohol stimulates the release of dopamine and serotonin in the nucleus accumbens.

The effects of acute IP administration (0.5, 1.0 or 2.0 g/kg) and local perfusion (25, 50 or 100 mM) of ethanol on the extracellular concentrations of dopamine (DA), serotonin (5-HT) and their metabolites in the nucleus accumbens (ACC) of the rat were studied with in vivo microdialysis coupled with a small-bore HPLC electrochemical detection procedure. The IP administration of 1.0 and 2.0 g/kg ethanol significantly (p less than 0.05) increased the extracellular levels of DA and 5-HT in the ACC whereas the 0.5 g/kg dose caused no change. In general, the extracellular levels of the 3 monoamine metabolites were not altered by IP ethanol except for a slight increase in the levels of homovanillic acid following the 2.0 g/kg dose. Local perfusion of 50 and 100 mM ethanol (but not 25 mM) through the microdialysis probe markedly increased (170-200% of control) the extracellular levels of DA in the ACC. Only the 100 mM concentration of ethanol altered the extracellular levels of 5-HT (2-fold increase), 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid. Addition of 100 microM ICS 205-930 (a 5-HT3 antagonist) to the perfusate markedly reduced the 100 mM ethanol-stimulated release of DA and 5-HT. Overall, the data suggest that ethanol can stimulate the release of both DA and 5-HT in the ACC and that the action of ethanol within the ACC may be mediated in part by 5-HT3 receptors.

3,4-Dihydroxyphenylacetic Acid↗

Densities of dopamine D2 receptors are reduced in CNS regions of alcohol-preferring P rats.

The densities of dopamine D2 recognition sites labelled with [3H]sulpiride were determined in the caudate-putamen, nucleus accumbens (medial and lateral portions), olfactory tubercle, substantia nigra (pars reticulata and pars compacta), and ventral tegmental area (VTA) of alcohol-naive, selectively bred P (N = 7) and NP (N = 7) rats using quantitative autoradiography. The binding of [3H]sulpiride was 20-25% lower (P < 0.05) in the caudate-putamen, medial and lateral nucleus accumbens, and VTA of the P compared with the NP rats. No significant differences were observed between the P and NP rats in the olfactory tubercle or substantia nigra. [3H]Sulpiride binding, using standard membrane preparations, established with Scatchard analysis that the difference in the densities of D2 recognition sites in the caudate-putamen between the P and NP rats was due to lower Bmax values for the P line. The results indicate that the number of dopamine D2 receptor sites is lower in several central nervous system regions of the P rats compared to NP rats.

Alcohol Drinking↗

Effects of D1 and D2 dopamine receptor agents on ethanol consumption in the high-alcohol-drinking (HAD) line of rats.

Dopamine receptor agonists and antagonists were tested for effects on alcohol drinking in female HAD rats (n = 10) given limited access (4 h/day) to a 10% (v/v) ethanol solution. Food and water were available ad libitum. Subcutaneous drug injections were given 30-60 min before the ethanol access periods. The D2 agonist quinpirole (0.04-2.0 mg/kg) caused a dose-dependent decrease in alcohol drinking throughout the 4-h period. Spiperone, a D2 antagonist, had no effect during the initial part of the session, but by the fourth hour, the 10 micrograms/kg dose tended to increase alcohol intake and the 30 micrograms/kg dose reduced intake. The D1 antagonist SCH-23390 (3-30 micrograms/kg) dose-dependently decreased ethanol drinking during the first hour of access. The D1 agonist SKF-38393 (2-6 mg/kg) also decreased alcohol intake, but it was less effective than SCH-23390. The findings implicate both D1 and D2 receptors in the reinforcing effects of alcohol drinking by the HAD line of rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Comparison of alcohol-preferring (P) and nonpreferring (NP) rats on tests of anxiety and for the anxiolytic effects of ethanol.

Rats of the selectively bred alcohol-preferring P and alcohol-nonpreferring NP lines were evaluated using three different behavioral measures of anxiety. Compared with NP rats, P rats (1) showed greater footshock-induced suppression of operant responding in an approach-avoidance conflict test; (2) spent less time in the open arms of an elevated plus maze; and (3) took longer in a passive avoidance test to step down from a platform to a grid floor where footshock was received 24 hours earlier. These findings indicate a greater degree of anxiety in the P than in the NP line of rats in these situations. Pretreatment with intraperitoneal (IP) ethanol (0.5-1.0 g/kg) injections produced anticonflict or anxiolytic effects in P but not in NP rats. However, the anticonflict effects of ethanol were small relative to those produced by chlordiazepoxide (CDP, 7.5 mg/kg) in both lines. The results demonstrate that selective breeding for divergent oral ethanol preference has produced associated differences between the P and NP lines of rats in behavioral tests of anxiety and in the anxiolytic effects of ethanol.

Alcohol Drinking↗

Serotonergic neurons in the alcohol preferring rats.

Previously, we have shown that the serotonin (5-HT) content and fiber density in a number of terminal brain regions have been found to be decreased in the selectively bred, alcohol preferring (P) rats than in the alcohol nonpreferring (NP) rats. In this study, we further report that, compared with NP rats, there were fewer 5-HT-immunostained (5-HT-IM) neurons in the major ascending raphe nuclei of the P rats. Among the three major groups of 5-HT neurons responsible for the majority of ascending projections to forebrain, dorsal raphe (B7), median raphe (B8), and B9, there were fewer 5-HT-IM neurons in the median and dorsal raphe (not including nucleus oralis) of P rats, compared with NP rats (unpaired Student's test). No difference was observed in the B9 group. When the animals were treated with pargyline and L-tryptophan to enhance the 5-HT in the neurons, the number of 5-HT-IM neurons increased in both lines of rats. However, the difference in the number of 5-HT neurons between the rat lines remained. The intensity of 5-HT-IM was also found to be lower in the dorsal raphe neurons of the untreated P than in the untreated NP rats. The decreased 5-HT-IM was supported by high performance liquid chromatography measurement of 5-HT content, which also indicated that 5-HT content of the dorsal raphe was lower in the P than in the NP rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Comparison of innate EEG parameters in rat lines selected for ethanol preference.

Through bidirectional selective breeding, lines of rats that differ greatly in their voluntary alcohol drinking behavior have been developed--namely, the alcohol-preferring (P) and high-alcohol-drinking (HAD) lines and the alcohol-nonpreferring (NP) and low-alcohol-drinking (LAD) lines. The present experiments were designed to determine if an association exists between ethanol preference and features of the electroencephalogram (EEG) during various sleep-wake behaviors. Of the EEG parameters measured, only theta activity in the hippocampus revealed differences in the lines. However, these differences were not generally associated with ethanol preference. The peak frequency and distribution mean of hippocampal theta activity during REM sleep were significantly higher in NP rats than in P, HAD, and LAD rats. In addition, theta frequency during alert immobility tended to be higher in NP rats than in P, HAD, and LAD rats. A qualitative comparison of these data with published data from unselected rats further suggested that the NP rats are uniquely different with respect to theta frequency.

Alcohol Drinking↗

Ethanol self-infusion into the ventral tegmental area by alcohol-preferring rats.

The ventral tegmental area (VTA) and its projections have been implicated in the reinforcing effects of drugs of abuse. Selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines of rats were used to evaluate the reinforcing actions of ethanol in the VTA using intracranial self-administration (ICSA) operant procedures. P rats self-administered nanoliter quantities of 50-200 mg% ethanol in artificial CSF directly into the VTA whereas NP rats had low levels of responding at these ethanol concentrations. Responses on the active lever were 50-fold higher for the P compared with the NP rats for the self-infusion of 150 mg% ethanol. NP rats responded at the same level on the active and inactive levers at all ethanol concentrations and had low responses/session (3 to 15 total responses) at all concentrations. Further, operant responding on the active lever was reduced when artificial CSF alone was substituted for 100 mg% ethanol, and responding on the active lever was reinstated when ethanol was returned. For one group of rats, an illuminated house light served as a discriminative stimulus, which signalled the availability of ICSA, while a cue light was paired with the onset of ethanol infusion. Extinction in the presence of these stimuli required 6-7 sessions. However, only 2-3 extinction sessions were necessary for another group trained without stimulus cues, suggesting that cues paired with the ICSA of ethanol can acquire conditioned reinforcing properties. The findings indicate that ethanol can act as a reinforcer when administered directly into the VTA.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Mesolimbic dopamine system in alcohol-preferring rats.

The mesolimbic dopamine system of the brain, in particular the nucleus accumbens (Acb), is long known to be involved in reward behavior. When compared with the alcohol-nonpreferring NP rats, the alcohol-preferring P rats exhibit lower dopamine (DA) levels in the Acb as well as in other forebrain areas (20). In the present study, the DA innervation density, as determined by tyrosine hydroxylase (TH) immunostaining, was found lower in the selective cingulum cortex and the shell of the Acb of the P compared with that of NP rats. These structures cluster in the medial aspect of the mesolimbic system. There were no differences in other major DA mesolimbic brain regions. The subpopulation of DA neurons in the ventral tegmental area (VTA) projecting to the Acb was found to be smaller in the P than in the NP rats, as shown by horseradish peroxidase tracing and TH immunocytochemistry double staining. However, the total number of the DA neurons in the VTA, the major mesolimbic DA center, was found to be similar in the P and NP rats. These results indicate a selective reduction of catecholaminergic innervation in the dopaminergic medial mesolimbic system in the P rats and suggest that the P and NP rat lines should be a useful model for the investigation of DA involvement in alcohol drinking as well as other reinforced behaviors.

Alcohol Drinking↗

Apomorphine and 7-OH DPAT reduce ethanol intake of P and HAD rats.

Adult male rats of the alcohol-preferring (P) line (N = 10) and high alcohol drinking (HAD) line (N = 12) were used to study the effects of IP administration of 0.125-0.50 mg/kg 7-OH DPAT (a putative D agonist) and 0.25-1.0 mg/kg apomorphine (a dopamine agonist with 50-fold higher affinities for the D1 and D2 receptors than for the D3 receptor) on the concurrent intakes of 10% (v/v) ethanol and 0.0125% (g/v) saccharin during a daily 4-h scheduled access period. Control intakes by the P rats for the 4-h period were 17.9 +/- 0.5 and 7.2 +/- 0.4 ml for the ethanol and saccharin solutions, respectively. For the HAD line, ethanol consumption was 18.7 +/- 0.2 ml and saccharin intake was 8.7 +/- 1.6 ml for the 4-h period. In terms of grams ethanol/kg body wt, the 4-h intakes were 2.2 +/- 0.2 for the P line and 3.0 +/- 0.3 for the HAD rats. Both P and HAD rats consumed approximately 40% of their total ethanol intake in the first 15 min of access while consuming only about 15% of their total saccharin intake during this 15-min period. The putative D3 agonist 7-OH DPAT produced a decrease in ethanol intake in the first h to 45-55% of control levels for the P rat (p < 0.01) and to 25-70% of control values in the HAD line (p < 0.001). Apomorphine caused a dose-dependent decrease in ethanol intake in the first hour to 15-70% of control values in the P rat (p < 0.001) and to 25-60% of control levels in the HAD line (p < 0.001). Saccharin and 4-h food intakes for both lines were not altered by either 7-OH DPAT or apomorphine. Overall, these results suggest that D2 and D3 dopamine receptors may play a role in mediating alcohol drinking behavior of the selectively bred HAD and P lines of rats.

Alcohol Drinking↗

Effects of ethanol consumption by adolescent alcohol-preferring P rats on subsequent behavioral performance in the cross-maze and slip funnel tests.

Neonatal alcohol exposure during the first 1-2 weeks of age is known to produce subsequent behavioral hyperactivity in rats. However, little is known about the effects of alcohol exposure during adolescence on subsequent adult behavior. In the present study, male and female P rats had free access to 10% alcohol during adolescence (3-8 weeks of age). After 8 days of abstinence, their behavior was evaluated in the cross-maze and in the inescapable slip funnel tests during the 10th week of age. Two-way ANOVAs revealed significant effects of alcohol drinking on several variables. Compared to alcohol-naive rats, the alcohol-exposed group started exploration earlier (3.5 +/- 0.3 vs. 5.4 +/- 0.7 s, p = 0.03) and made fewer defecations. In the slip funnel test, the alcohol group spent more time immobile (130 +/- 7 vs. 107 +/- 5 s, p = 0.01) and less time attempting to escape out of the funnel (11 +/- 2 vs. 28 +/- 5 s, p = 0.002) than the control group. Overall, the results suggest that the effects of alcohol drinking by P rats during adolescence on subsequent behavior are to reduce novelty-induced anxiety (cross-maze test) and lower response to stress induced by an inescapable situation (slip-funnel test).

Aging↗

Long-term effects of alcohol drinking on cerebral glucose utilization in alcohol-preferring rats.

The 2-[14C]deoxyglucose (2-DG) quantitative autoradiography technique was used to determine rates of local cerebral glucose utilization (LCGU) in discrete brain regions in alcohol-chronic (A-C), alcohol-deprived (A-D) and alcohol-naïve (A-N) adult, male alcohol-preferring (P) rats. The hypothesis to be tested is that neuronal alterations occur as a result of chronic alcohol drinking and some of these alterations persist for long periods in the absence of alcohol. Following 6 weeks of daily 4-h scheduled access sessions to 15% (v/v) ethanol and water, group A-D received only water during the sessions over the next 2 weeks, whereas groups A-C and A-N continued to receive ethanol-water and water-water, respectively. On the 14th day of the deprivation interval, LCGU rates were measured 1 h prior to the scheduled access period. Mean ethanol intake for the A-D and A-C groups was 1.5+/-0.1 g ethanol/kg body weight per 4 h. LCGU rates were significantly decreased in 49 of 57 regions or subregions examined in the A-C group compared to the A-N group, including subregions of the cerebral cortex, hippocampus and structures in the mesocorticolimbic and nigrostriatal systems. Following alcohol deprivation, LCGU values in the A-D group were partially or completely returned to A-N levels in many, but not all, regions. In several limbic regions (e.g., ventral tegmental area, olfactory tubercle, medial prefrontal cortex, ventral pallidum and lateral septum), no recovery of LCGU rates was observed after 2 weeks of alcohol deprivation. This study demonstrates that chronic alcohol consumption produces significant reductions in functional neuronal activity in P rats, some of which persist in the absence of ethanol. The extent to which LCGU rates returned to normal levels following 2 weeks of alcohol deprivation varied among brain regions, suggesting that there are imbalanced interactions among and within several CNS sites, which do not reflect either the alcohol-naïve or chronic alcohol-exposed state. Such neuronal imbalances may underlie relapse of alcohol drinking following prolonged abstinence.

Alcohol Drinking↗

Effects of amphetamine on locomotor activity in adult and juvenile alcohol-preferring and -nonpreferring rats.

The objective of this study was to determine whether functional differences exist in amphetamine-induced locomotor activity between alcohol-naive alcohol-preferring (P) and -nonpreferring (NP) rats during postnatal development and during adulthood. Using a between-subjects design, 20- and 28-day-old P and NP rats (male and female counterbalanced, n=11-16/line) were habituated for 30 min in a photocell activity field. Each rat received subcutaneous injections of saline or 0.3, 0.6 or 1.2 mg/kg d-amphetamine (AMPH) and were then tested for an additional 30 min. Because of age and line differences in basal locomotor activity, total activity counts during the 30-min postdrug period were standardized using Z-score transformations. In the 20- and 28-day-old rats, dose-dependent locomotor activity increases after AMPH injections were obtained at both ages, although activity levels were greater in the 20-day-old pups. The 20-day-old female NP rats showed greater AMPH-induced increases in locomotor activity than P rats, whereas at 28 days of age, male NP rats showed greater activity levels than P rats to AMPH. For the adult P and NP rats (n=8/line/gender), a within-subject design was used. In the adults, the NP line had higher locomotor activity than the P line following AMPH injection, and male rats were activated more by AMPH than female rats. The results suggest that functioning of the DA system in the adult P line is reduced compared to the adult NP line, and this line difference is also observed to some degree at an early postweaning developmental period.

Aging↗

Ethanol-stimulated serotonin release in the ventral hippocampus: an absence of rapid tolerance for the alcohol-preferring P rat and insensitivity in the alcohol-nonpreferring NP rat.

This study examined the acute effects of intraperitoneal administration of ethanol on the extracellular levels of serotonin (5-HT) in the ventral hippocampus (vHIP) of adult, male alcohol-preferring P and -nonpreferring NP rats. Using in vivo microdialysis coupled with HPLC and electrochemical detection, the effects of acute administration of saline or 1.0, 1.75, or 2.5 g/kg ethanol on the extracellular levels of 5-HT in the vHIP were examined. Saline and 1.0 g/kg ethanol did not alter the extracellular levels of 5-HT. However, the 1.75-g/kg dose resulted in a transient increase in 5-HT levels in the vHIP of P rats only. Administration of 2.5 g/kg ethanol increased 5-HT levels to 180% of baseline in P rats (P<.05), but was without effect on NP rats. The 2.5-g/kg dose also significantly increased the extracellular levels of 5-HT in the vHIP of P rats, which had been pretreated with the same dose of ethanol 18-24 h earlier (P<.05). Comparison of the response of ethanol pretreated P rats with animals that had been pretreated with saline 24 h earlier did not reveal any significant differences in ethanol-stimulated increases in 5-HT levels between the groups. These data suggest that ethanol may activate terminals of the median raphe 5-HT system in P rats because the vHIP receives its 5-HT inputs primarily from the median raphe nucleus (MRN). Rapid tolerance does not develop to this activation of the system in the vHIP of P rats. In addition, the data suggest that the 5-HT system in the vHIP of NP rats may be relatively insensitive to the stimulating effect of acute ethanol of 5-HT release.

Alcohol Drinking↗

Immunostained serotonergic fibers are decreased in selected brain regions of alcohol-preferring rats.

The levels of serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) are decreased in the hippocampus, nucleus accumbens, and cortex of selectively bred alcohol-preferring (P) rats, compared with the alcohol-nonpreferring (NP) rats. In this study, we have confirmed these findings by immunocytochemistry and quantitative image analysis which indicates that there is a reduction of 5-HT immunostained fibers in several brain areas of alcohol-naive P rats. Three major areas possibly related to alcohol drinking, hippocampus, accumbens, and cortex, were examined. Pathways to these areas were also examined. The 5-HT fiber bundles had the same pattern in P and NP rats. However, in the terminal regions of the ventral hippocampus, the amount of 5-HT fibers was reduced in P rats as compared with NP rats. The 5-HT fibers in the hilus and CA4 of the dentate gyrus were also significantly decreased in the P rats. No differences in fiber density were seen in the anterior nucleus accumbens, but a significant decrease was seen in the middle medial and posterior accumbens of P rats. In the cortical regions examined, decreases in 5-HT fibers were observed in the posterior cingulum and anterior frontal cortex, but not in the insular frontal cortex of P rats. These observations indicate that there are quantitative decreases in 5-HT innervations or that the 5-HT in some 5-HT fibers is reduced to a level undetectable by immunocytochemistry in the brains of P rats when compared with that of NP rats.

Animals↗

Regional CNS densities of monoamine receptors in alcohol-naive alcohol-preferring P and -nonpreferring NP rats.

The densities of subtypes of serotonin (5-HT) and dopamine (DA) receptors were determined in the CNS of alcohol-naive alcohol-preferring P and -nonpreferring NP lines of rats. Autoradiography studies were undertaken to measure the densities of 5-HT1B sites labelled with 100 pM [125I](-)-iodocyanopindolol, 5-HT3 sites labelled with 2 nM [3H]LY 278584, and D1 sites labelled with 1 nM[3H]SCH 23390. Membrane binding, using tissue combined from the olfactory bulb, olfactory tubercle, and nucleus accumbens, was carried out to determine Kd and B max values for the binding of 0.25-8.0 nM[3H]7-OH DPAT to D3 sites. Among the 48 regions measured for differences in 5-HT1B recognition sites, statistically significant differences (p < 0.05) were found only in the cingulate and retrosplenial cortices, in the lateral and medial septum, and in the lateral nucleus of the amygdala, with lower values being found in the P than the NP line. There were no significant differences in the regional CNS densities of D1 or 5-HT3 sites between the P and NP lines. There were also no differences between the rat lines in the Kd or Bmax values for [3H]7-OH DPAT binding to D3 sites. The lower densities of 5-HT1B sites in the CNS of the P compared to the NP rats may be a result of reduced numbers of 5-HT1B presynaptic autoreceptors as well as postsynaptic receptors in the P line. The observation that there are no differences in the amount of radioligand binding to D1, 5-HT3, and D3 sites between the P and NP lines suggests that the disparate alcohol drinking behaviors of these two lines is not associated with an innate alteration in the densities of these receptor subtypes.

Animals↗

Regional CNS densities of serotonin and dopamine receptors in high alcohol-drinking (HAD) and low alcohol-drinking (LAD) rats.

The densities of subtypes of serotonin (5-HT) and dopamine (DA) receptors were determined in the CNS of male alcohol-naive HAD and LAD lines of rats. Autoradiographic studies were undertaken to measure the densities of (a) 5-HT1A sites labelled with 2 nM [3H]8-OH DPAT, (b) 5-HT2A sites labelled with 2 nM [3H] ketanserin, (c) D1 sites labelled with 1 nM [3H]SCH23390, and (d) D2 sites labelled with 20 nM [3H]sulpiride. Membrane binding, using tissue combined from the olfactory bulb, olfactory tubercle, and nucleus accumbens, was carried out to determine Kd and Bmax values for the binding of 0.25-8.0 nM [3H]7-OH DPAT to D3 sites. Among the 14 regions measured for densities of 5-HT1A sites, no interline differences were found in the cerebral cortical regions or in the septal nuclei; however, within the hippocampus, 15-20% lower binding of [3H]8-OH DPAT was observed in the posterior dorsal CA3 and dentate gyrus of the HAD line. There were no interline differences in any of the 10 regions examined for [3H]ketanserin binding to 5-HT2A sites, or in the densities of D1 and D2 sites in the mesolimbic and nigrostriatal DA systems, except for a 35% higher density of D2 sites in the substantia nigra pars compacta of the HAD line. There were no interline differences in the Kd or Bmax values for [3H]7-OH DPAT binding to D3 sites. Overall, these results indicate that no marked interline differences are evident in the densities of 5-HT1A, 5-HT2A, D1, D2, and D3 receptors within the mesolimbic system that could be associated with the disparate alcohol drinking behaviors of the HAD and LAD rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗