Limits...
The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats.

Haile CN, Hao Y, O'Malley PW, Newton TF, Kosten TA - Brain Sci (2012)

Bottom Line: The high dose (1.0 mg/kg), but not the low dose (0.3 mg/kg) of DOX significantly decreased the development and expression of COC sensitization.DOX alone did not differ from saline.These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine's behavioral effects.

View Article: PubMed Central - PubMed

Affiliation: Michael E. DeBakey VA Medical Center, Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA. chaile@bcm.edu.

ABSTRACT
Medications that target norepinephrine (NE) neurotransmission alter the behavioral effects of cocaine and may be beneficial for stimulant-use disorders. We showed previously that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats and doxazosin (DOX), a longer-acting α1 antagonist blocked cocaine's subjective effects in cocaine-dependent volunteers. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6-8) were administered saline, cocaine (COC, 10 mg/kg) or DOX (0.3 or 1.0 mg/kg) alone or in combination for 5 consecutive days (development). Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression). COC increased locomotor activity across days indicative of sensitization. The high dose (1.0 mg/kg), but not the low dose (0.3 mg/kg) of DOX significantly decreased the development and expression of COC sensitization. DOX alone did not differ from saline. These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine's behavioral effects. Results also suggest that blockade of both the development and expression of locomotor sensitization may be important characteristics of possible pharmacotherapies for cocaine dependence in humans.

No MeSH data available.


Related in: MedlinePlus

The development of cocaine locomotor sensitization is presented as mean ± standard error of mean (SEM) locomotor activity assessed as (A) distance traveled (cm) and (B) vertical counts over 5 consecutive days of drug treatments. Groups of rats (N) were administered vehicle (○), cocaine (●, COC; 10 mg/kg; intraperitoneally, IP), doxazosin (□, DOX; 0.3 or Δ, 1.0 mg/kg, IP), or the combination of DOX 0.3 (■) and 1.0 (▲) plus COC. DOX alone did not affect gross locomotor activity compared to saline. DOX (1.0 mg/kg) significantly blocked the development of COC-induced increases in vertical counts (B) across days.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4061810&req=5

brainsci-02-00619-f001: The development of cocaine locomotor sensitization is presented as mean ± standard error of mean (SEM) locomotor activity assessed as (A) distance traveled (cm) and (B) vertical counts over 5 consecutive days of drug treatments. Groups of rats (N) were administered vehicle (○), cocaine (●, COC; 10 mg/kg; intraperitoneally, IP), doxazosin (□, DOX; 0.3 or Δ, 1.0 mg/kg, IP), or the combination of DOX 0.3 (■) and 1.0 (▲) plus COC. DOX alone did not affect gross locomotor activity compared to saline. DOX (1.0 mg/kg) significantly blocked the development of COC-induced increases in vertical counts (B) across days.

Mentions: Figure 1A,B shows locomotor activity and vertical counts on the habituation day (HAB) before treatments were begun and the effects of DOX on the development (Days 1–5) of cocaine-induced locomotor sensitization. Although not readily apparent from the figure, the DOX groups differed in baseline distances traveled on the HAB day before the start of the experiment. This statement is supported by a significant main effect for DOX group (F(2,37) = 14.04, p < 0.0001). Specifically, the two groups that would be administered the higher dose of DOX showed lower locomotor activity on the habituation day compared to the other groups, p < 0.01. There was no difference across COC groups, p > 0.10. Due to these baseline effects, data were also analyzed using Analysis of Co-variance (ANOCOVA). Distance traveled was greater among groups that received COC on Day 1 compared to the saline group. This is supported by a significant main effect for treatment among groups (F(1,37) = 34.66, p < 0.001). Pair-wise multiple comparisons revealed no differences among groups that received DOX alone and saline (ps > 0.05). Close examination of Figure 1 (Day 1) does show however, that the DOX 0.3 + COC treated group traveled greater distance than DOX 0.3 alone (p < 0.05).


The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats.

Haile CN, Hao Y, O'Malley PW, Newton TF, Kosten TA - Brain Sci (2012)

The development of cocaine locomotor sensitization is presented as mean ± standard error of mean (SEM) locomotor activity assessed as (A) distance traveled (cm) and (B) vertical counts over 5 consecutive days of drug treatments. Groups of rats (N) were administered vehicle (○), cocaine (●, COC; 10 mg/kg; intraperitoneally, IP), doxazosin (□, DOX; 0.3 or Δ, 1.0 mg/kg, IP), or the combination of DOX 0.3 (■) and 1.0 (▲) plus COC. DOX alone did not affect gross locomotor activity compared to saline. DOX (1.0 mg/kg) significantly blocked the development of COC-induced increases in vertical counts (B) across days.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061810&req=5

brainsci-02-00619-f001: The development of cocaine locomotor sensitization is presented as mean ± standard error of mean (SEM) locomotor activity assessed as (A) distance traveled (cm) and (B) vertical counts over 5 consecutive days of drug treatments. Groups of rats (N) were administered vehicle (○), cocaine (●, COC; 10 mg/kg; intraperitoneally, IP), doxazosin (□, DOX; 0.3 or Δ, 1.0 mg/kg, IP), or the combination of DOX 0.3 (■) and 1.0 (▲) plus COC. DOX alone did not affect gross locomotor activity compared to saline. DOX (1.0 mg/kg) significantly blocked the development of COC-induced increases in vertical counts (B) across days.
Mentions: Figure 1A,B shows locomotor activity and vertical counts on the habituation day (HAB) before treatments were begun and the effects of DOX on the development (Days 1–5) of cocaine-induced locomotor sensitization. Although not readily apparent from the figure, the DOX groups differed in baseline distances traveled on the HAB day before the start of the experiment. This statement is supported by a significant main effect for DOX group (F(2,37) = 14.04, p < 0.0001). Specifically, the two groups that would be administered the higher dose of DOX showed lower locomotor activity on the habituation day compared to the other groups, p < 0.01. There was no difference across COC groups, p > 0.10. Due to these baseline effects, data were also analyzed using Analysis of Co-variance (ANOCOVA). Distance traveled was greater among groups that received COC on Day 1 compared to the saline group. This is supported by a significant main effect for treatment among groups (F(1,37) = 34.66, p < 0.001). Pair-wise multiple comparisons revealed no differences among groups that received DOX alone and saline (ps > 0.05). Close examination of Figure 1 (Day 1) does show however, that the DOX 0.3 + COC treated group traveled greater distance than DOX 0.3 alone (p < 0.05).

Bottom Line: The high dose (1.0 mg/kg), but not the low dose (0.3 mg/kg) of DOX significantly decreased the development and expression of COC sensitization.DOX alone did not differ from saline.These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine's behavioral effects.

View Article: PubMed Central - PubMed

Affiliation: Michael E. DeBakey VA Medical Center, Menninger Department of Psychiatry &amp; Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA. chaile@bcm.edu.

ABSTRACT
Medications that target norepinephrine (NE) neurotransmission alter the behavioral effects of cocaine and may be beneficial for stimulant-use disorders. We showed previously that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats and doxazosin (DOX), a longer-acting α1 antagonist blocked cocaine's subjective effects in cocaine-dependent volunteers. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6-8) were administered saline, cocaine (COC, 10 mg/kg) or DOX (0.3 or 1.0 mg/kg) alone or in combination for 5 consecutive days (development). Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression). COC increased locomotor activity across days indicative of sensitization. The high dose (1.0 mg/kg), but not the low dose (0.3 mg/kg) of DOX significantly decreased the development and expression of COC sensitization. DOX alone did not differ from saline. These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine's behavioral effects. Results also suggest that blockade of both the development and expression of locomotor sensitization may be important characteristics of possible pharmacotherapies for cocaine dependence in humans.

No MeSH data available.


Related in: MedlinePlus