Neurotensin Gene Expression and Behavioral Responses Following Administration of Psychostimulants and Antipsychotic Drugs in Dopamine D3 Receptor Deficient Mice

Abstract

Exposure to psychostimulants and antipsychotics increases neurotensin (NT) gene expression in the striatum

Dose–response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine

“…Specifically, a low cocaine dose (5 mg/kg) produced significantly greater locomotor activity in D3R mutant mice relative to wild-type mice, whereas higher doses (10-40 mg/kg) produced comparable alterations in both locomotor activity and stereotypy in D3R and wild-type mice (Betancur et al, 2001;Carta et al, 2000;Xu et al, 1997). Collectively, these findings add to a growing body of evidence that support the model that D3R plays an inhibitory role in psychostimulant-induced locomotor activity, but not stereotypy, in a dose-dependent manner.…”

“…At the behavioral level, the originally described increased spontaneous locomotor activity exhibited by D3R mutant mice (Accili et al, 1996;Xu et al, 1997) has been replicated by some studies (Betancur et al, 2001;Boulay et al, 1999;Vallone et al, 2002) but not others (Joseph et al, 2002;Jung et al, 1999;McNamara et al, 2002). A significant increase in novelty-induced stereotypy has also been observed in D3R mutant mice relative to wild-type controls (Joseph et al, 2002).…”

“…With regard to psychostimulant-induced locomotor activity, acute cocaineinduced locomotor activity was significantly greater in D3R mutant mice relative to wild-type mice at the lowest dose (5 mg/kg) tested; however, this effect was not observed at higher doses (10-40 mg/kg) (Xu et al, 1997). Subsequent studies have similarly observed that higher doses of acute cocaine (20-30 mg/kg) produce comparable elevations in locomotor activity in D3R mutant and wild-type mice (Betancur et al, 2001;Carta et al, 2000). Repeated treatment with high dose cocaine (25 mg/kg twice daily) also increased stereotypy and reduced locomotor activity to a greater degree in D3R mutant mice than in wild-type mice (Carta et al, 2000), while a second study observed similar effects on stereotypy and locomotor activity in D3R mutant mice and wild-type animals in response to repeated cocaine treatment (20 mg/kg/day) (Betancur et al, 2001).…”

“…Subsequent studies have similarly observed that higher doses of acute cocaine (20-30 mg/kg) produce comparable elevations in locomotor activity in D3R mutant and wild-type mice (Betancur et al, 2001;Carta et al, 2000). Repeated treatment with high dose cocaine (25 mg/kg twice daily) also increased stereotypy and reduced locomotor activity to a greater degree in D3R mutant mice than in wild-type mice (Carta et al, 2000), while a second study observed similar effects on stereotypy and locomotor activity in D3R mutant mice and wild-type animals in response to repeated cocaine treatment (20 mg/kg/day) (Betancur et al, 2001). Cocaine and amphetamine (AMPH) have overlapping, but distinct, mechanisms of action (reviewed in Riddle et al, 2005), and to date there have been no published studies evaluating AMPH-induced locomotor activity and stereotypy in wild-type and D3R mutant mice.…”

7-OH-DPAT and PD 128907 Selectively Activate the D3 Dopamine Receptor in a Novel Environment

“…The earliest reports describing the highly restricted localization of D3 receptor expression suggested a potential role in psychosis (Sokoloff et al, 1990(Sokoloff et al, , 1992. Additionally, D3 receptor function is of particular interest because evidence suggests its effects are primarily inhibitory (Accili et al, 1996;Flores et al, 1996;Xu et al, 1997;Ekman et al, 1998;Menalled et al, 1999;Betancur et al, 2001), and that loss of this inhibitory function might contribute pathologically to neuropsychiatric disease (Flores et al, 1996;Richtand et al, 2001a, b).…”