Home cage observations following acute and repeated IV cocaine in intact and gonadectomized rats

Harrod, Steven B.; Mactutus, Charles F.; Browning, Catherine E.; Welch, M.A.; Booze, Rosemarie M.

doi:10.1016/j.ntt.2005.07.004

Cited by 7 publications

(8 citation statements)

References 27 publications

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“…No Tat effect was noted on activity in the center, locomotor incidence, or the orofacial measure of activity. Similar to previous research, repeated IV cocaine resulted in robust behavioral sensitization as indexed by automated and observed measures of locomotor activity (Wallace et al, 1996; Booze et al, 1999b; Harrod et al, 2005a; 2005b); however, prior Tat exposure attenuated the development of cocaine-induced behavioral sensitization. We investigated the effects of Tat-induced damage to the N Acc to better understand how HIV related proteins alter the behavioral effects of IV COC.…”

Section: Discussionsupporting

confidence: 82%

“…An observer, unaware of the treatment condition of the animal, observed and recorded the animal’s behavior, using a well-established protocol (Harrod et al, 2004; Harrod et al, 2005a; 2005b). Previous research by Booze et al (1997) determined that a 3.0 mg/kg/injection of cocaine resulted in peak arterial plasma levels within one-min of IV administration.…”

Section: Methodsmentioning

confidence: 99%

“…The dose of cocaine hydrochloride (3.0 mg/kg/day; Sigma, St. Louis, MO) was calculated on the weight of the salt and dissolved in saline immediately prior to injection in a volume of 1 ml/kg. The injection rate used in the present experiment was used in the previous pharmacokinetic analysis (Booze et al, 1997) and is within the duration shown to produce moderate-to-robust behavioral sensitization to psychostimulant drugs (Booze et al, 1999a;Booze et al, 1999b; Harrod et al, 2004; 2005a; 2005b; Samaha et al, 2002; Wallace et al, 1996). The IV dosing regimen used in the present experiment has been shown to produce arterial drug concentrations and a pharmacokinetic profile in rats similar to levels demonstrated in human cocaine volunteers (Booze et al, 1997; Evans et al, 1996), and has been associated with producing reinforcing and euphoric effects in humans (Fischman and Schuster, 1982).…”

Section: Methodsmentioning

confidence: 99%

“…Rats were microinjected with Tat or VEH, and the behavioral response to acute and repeated IV cocaine (or saline) was measured on days 1 and 14, respectively, using automated activity chambers and a behavioral observation method previously described (Booze et al, 1999a; Fray et al, 1980; Harrod et al, 2004; 2005a; 2005b; Wallace et al, 1996). The aim of this experiment was to examine the effect of Tat microinjection on the behavioral response to acute and repeated IV cocaine in order to determine if intra-accumbal Tat alters cocaine-mediated behavior.…”

Section: Introductionmentioning

confidence: 99%

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Intra-accumbal Tat1–72 alters acute and sensitized responses to cocaine

Harrod

Mactutus

Fitting

et al. 2008

Pharmacology Biochemistry and Behavior

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The effects of Tat, an HIV-1 protein, on intravenous cocaine-induced locomotor activity were examined in ovariectomized rats. Animals were habituated to activity chambers, administered an IV baseline/saline injection, and 24 h later, received bilateral, intra-accumbal microinjections of Tat1-72 (15 μg/μl) or vehicle. Twenty four hours later, rats received the first of 14 daily IV cocaine injections (3.0 mg/kg/inj, 1/day) or saline. Locomotor activity was measured in automated chambers for 30 min following baseline and after the 1st and 14th cocaine injections. Observational time sampling following cocaine was also performed. Following acute cocaine/saline, Tat significantly increased cocaine-induced total activity over the 30-min session, with no significant effects for activity in the central compartment. Repeated cocaine injections produced behavioral sensitization with ~2-fold higher levels of total activity, ~3-fold higher levels of centrally directed activity, and increased locomotor scores via direct observations. Following repeated cocaine/saline, Tat altered the development of cocaine-induced behavioral sensitization for total activity with prior Tat exposure attenuating the development of cocaine-induced sensitization. Collectively, these data show that bilateral microinjection of Tat into the N Acc alters IV cocaine-induced behavior, suggesting that Tat may produce behavioral changes by disrupting the mesocorticolimbic pathway.

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Section: Discussionsupporting

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intra-accumbal Tat1–72 alters acute and sensitized responses to cocaine

Harrod

Mactutus

Fitting

et al. 2008

Pharmacology Biochemistry and Behavior

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“…It could be argued that these discrepancies result from differences strain of rats used [33], route of cocaine administration [30, 31], and/or the behavioral parameter assessed [26], among others. However, we consider that the dose of cocaine used is of the utmost importance.…”

Section: Discussionmentioning

confidence: 99%

Testosterone is essential for cocaine sensitization in male rats

Menéndez‐Delmestre

Segarra

2011

Physiology & Behavior

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Most studies agree that males and females respond differently to drugs of abuse. In females, estradiol enhances the behavioral response to cocaine. However, studies on the role of testosterone and the locomotor response to psychostimulants in the male rat are inconclusive. Our study was designed to determine the behavioral effects of testosterone on the development and persistence of cocaine sensitization in male rats. We tested different doses of cocaine (10, 15 and 30mg/kg) to determine which dose induced locomotor sensitization in intact (INT) and gonadectomized (GDX) animals. We also investigated if GDX males with testosterone replacement (GDX-T) showed a similar locomotor response to cocaine as INT males. Our data showed that gonadectomy enhanced the locomotor response to a single cocaine injection. This effect was not observed in gonadectomized rats that received testosterone replacement. However, GDX rats did not show a progressive increase in their locomotor response to repeated cocaine administration (15 and 30 mg/kg) (sensitization) as did INT and GDX-T animals. It is possible that in GDX males, the initial high locomotor response to cocaine creates a ceiling effect that limits further increase in cocaine-induced hyperactivity. These findings indicate that testosterone not only modulates the behavioral response to a single and to repeated cocaine injections, but is essential for male rats to become sensitized to cocaine.

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